Physiology of the orexinergic/hypocretinergic system: A revisit in 2012

American Journal of Physiology - Cell Physiology

Volumn 304, Issue 1, 2013, Pages

  Kukkonen, Jyrki P ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

G protein coupled receptor; Neuropeptide; Orexin receptor; OX1 receptor; OX2 receptor

Indexed keywords

1 (2 METHYL 6 BENZOXAZOLYL) 3 (1,5 NAPHTHYRIDIN 4 YL)UREA; 1 (6,8 DIFLUORO 2 METHYL 4 QUINOLINYL) 3 (4 DIMETHYLAMINOPHENYL)UREA; CALCIUM ION; ENDOCANNABINOID; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; MESSENGER RNA; MUTANT PROTEIN; OREXIN; OREXIN 1 RECEPTOR; OREXIN 2 RECEPTOR; OREXIN A; OREXIN B; RECEPTOR BLOCKING AGENT; SB 41022; SB 410220; SB 674042; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ADRENAL GLAND; AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CELL DEATH; CENTRAL NERVOUS SYSTEM; DRUG TARGETING; FOOD INTAKE; GASTROINTESTINAL TRACT; GENITAL SYSTEM; HEMATOPOIETIC CELL; HUMAN; HYPOPHYSIS; INTRACELLULAR SIGNALING; ION TRANSPORT; LIGAND BINDING; MEDICAL LITERATURE; METABOLIC REGULATION; NERVE CELL; NONHUMAN; OREXINERGIC NERVE CELL; OREXINERGIC SYSTEM; PANCREAS ISLET; PLASTICITY; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REVIEW; SLEEP; SYMPATHETIC FUNCTION; WAKEFULNESS;

AMINO ACID SEQUENCE; ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MOLECULAR SEQUENCE DATA; NEUROPEPTIDES; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROPEPTIDE; SIGNAL TRANSDUCTION;

EID: 84871860395     PISSN: 03636143     EISSN: 15221563     Source Type: Journal    
DOI: 10.1152/ajpcell.00227.2012     Document Type: Review

References (415)

1. Abrahamson EE, Leak RK, Moore RY. The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12: 435-440, 2001.
2. Acuna-Goycolea C, van den Pol A. Glucagon-like peptide 1 excites hypocretin/orexin neurons by direct and indirect mechanisms: implications for viscera-mediated arousal. J Neurosci 24: 8141-8152, 2004.
3. Acuna-Goycolea C, van den Pol AN. Neuroendocrine proopiomelanocortin neurons are excited by hypocretin/orexin. J Neurosci 29: 1503-1513, 2009.
4. Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450: 420-424, 2007.
5. Adeghate E, Fernandez-Cabezudo M, Hameed R, El-Hasasna H, El Wasila M, Abbas T, Al-Ramadi B. Orexin-1 receptor co-localizes with pancreatic hormones in islet cells and modulates the outcome of streptozotocin-induced diabetes mellitus. PLos One 5: e8587, 2010.
6. Adeghate E, Hameed R. Mechanism of orexin B-stimulated insulin and glucagon release from the pancreas of normal and diabetic rats. Pancreas 40: 131-136, 2011.
7. Al-Barazanji KA, Wilson S, Baker J, Jessop DS, Harbuz MS. Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats. J Neuroendocrinol 13: 421-424, 2001.
8. Alvarez CE, Sutcliffe JG. Hypocretin is an early member of the incretin gene family. Neurosci Lett 324: 169-172, 2002.
9. Ammoun S, Holmqvist T, Shariatmadari R, Oonk HB, Detheux M, Parmentier M, Åkerman KE, Kukkonen JP. Distinct recognition of OX1 and OX2 receptors by orexin peptides. J Pharmacol Exp Ther 305: 507-514, 2003.
10. 2+ influx in OX1 receptor signaling. Mol Endocrinol 20: 80-99, 2006.
11. Ammoun S, Johansson L, Åkerman KEO, Korhonen L, Lindholm D, Kukkonen JP. Regulation of MAP/SAP-kinase cascades by orexin receptors (Abstract). Neuroscience 2003 Abstract 161.14: 2003.
12. Ammoun S, Lindholm D, Wootz H, Åkerman KE, Kukkonen JP. G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase. J Biol Chem 281: 834-842, 2006.
13. Anaclet C, Parmentier R, Ouk K, Guidon G, Buda C, Sastre JP, Akaoka H, Sergeeva OA, Yanagisawa M, Ohtsu H, Franco P, Haas HL, Lin JS. Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J Neurosci 29: 14423-14438, 2009.
14. Annerbrink K, Westberg L, Olsson M, Andersch S, Sjodin I, Holm G, Allgulander C, Eriksson E. Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene. Psychiatr Genet 21: 85-89, 2011.
15. Arrigoni E, Mochizuki T, Scammell TE. Activation of the basal forebrain by the orexin/hypocretin neurones. Acta Physiol (Oxf) 198: 223-235, 2010.
16. Asahi S, Egashira S, Matsuda M, Iwaasa H, Kanatani A, Ohkubo M, Ihara M, Morishima H. Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B. Bioorg Med Chem Lett 13: 111-113, 2003.
17. Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA. Lateral hypothalamic orexin/ hypocretin neurons: a role in reward-seeking and addiction. Brain Res 1314: 74-90, 2010.
18. Azhdari Zarmehri H, Semnanian S, Fathollahi Y, Erami E, Khakpay R, Azizi H, Rohampour K. Intra-periaqueductal gray matter microinjection of orexin-A decreases formalin-induced nociceptive behaviors in adult male rats. J Pain 12: 280-287, 2011.
19. Baier PC, Hallschmid M, Seeck-Hirschner M, Weinhold SL, Burkert S, Diessner N, Göder R, Aldenhoff JB, Hinze-Selch D. Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Sleep Med 12: 941-946, 2011.
20. Barb CR, Matteri RL. Orexin-B modulates luteinizing hormone and growth hormone secretion from porcine pituitary cells in culture. Domest Anim Endocrinol 28: 331-337, 2005.
21. Barreiro ML, Pineda R, Gaytan F, Archanco M, Burrell MA, Castellano JM, Hakovirta H, Nurmio M, Pinilla L, Aguilar E, Toppari J, Dieguez C, Tena-Sempere M. Pattern of orexin expression and direct biological actions of orexin-a in rat testis. Endocrinology 146: 5164-5175, 2005.
22. Barreiro ML, Pineda R, Navarro VM, Lopez M, Suominen JS, Pinilla L, Senaris R, Toppari J, Aguilar E, Dieguez C, Tena-Sempere M. Orexin 1 receptor messenger ribonucleic acid expression and stimulation of testosterone secretion by orexin-A in rat testis. Endocrinology 145: 2297-2306, 2004.
23. Bayer L, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M, Serafin M. Selective action of orexin (hypocretin) on nonspecific thalamocortical projection neurons. J Neurosci 22: 7835-7839, 2002.
24. Bayer L, Eggermann E, Serafin M, Grivel J, Machard D, Muhlethaler M, Jones BE. Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices. Neuroscience 130: 807-811, 2005.
25. Bayer L, Eggermann E, Serafin M, Saint-Mleux B, Machard D, Jones B, Muhlethaler M. Orexins (hypocretins) directly excite tuberomammillary neurons. Eur J Neurosci 14: 1571-1575, 2001.
26. Bayer L, Mairet-Coello G, Risold PY, Griffond B. Orexin/hypocretin neurons: chemical phenotype and possible interactions with melaninconcentrating hormone neurons. Regul Pept 104: 33-39, 2002.
27. Bayer L, Serafin M, Eggermann E, Saint-Mleux B, Machard D, Jones BE, Muhlethaler M. Exclusive postsynaptic action of hypocretinorexin on sublayer 6b cortical neurons. J Neurosci 24: 6760-6764, 2004.
28. Bengtsson MW, Makela K, Sjoblom M, Uotila S, Akerman KE, Herzig KH, Flemstrom G. Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A. Am J Physiol Gastrointest Liver Physiol 293: G501-G509, 2007.
29. Bergman JM, Roecker AJ, Mercer SP, Bednar RA, Reiss DR, Ransom RW, Meacham Harrell C, Pettibone DJ, Lemaire W, Murphy KL, Li C, Prueksaritanont T, Winrow CJ, Renger JJ, Koblan KS, Hartman GD, Coleman PJ. Proline bis-amides as potent dual orexin receptor antagonists. Bioorg Med Chem Lett 18: 1425-1430, 2008.
30. Bernard R, Lydic R, Baghdoyan HA. Hypocretin-1 activates G proteins in arousal-related brainstem nuclei of rat. Neuroreport 13: 447-450, 2002.
31. Bernard R, Lydic R, Baghdoyan HA. Hypocretin-1 causes G protein activation and increases ACh release in rat pons. Eur J Neurosci 18: 1775-1785, 2003.
32. Berthoud HR, Patterson LM, Sutton GM, Morrison C, Zheng H. Orexin inputs to caudal raphe neurons involved in thermal, cardiovascular, and gastrointestinal regulation. Histochem Cell Biol 123: 147-156, 2005.
33. Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E. The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia. Sleep 35: 1097-1104, 2012.
34. Beuckmann CT, Sinton CM, Williams SC, Richardson JA, Hammer RE, Sakurai T, Yanagisawa M. Expression of a poly-glutamineataxin- 3 transgene in orexin neurons induces narcolepsy-cataplexy in the rat. J Neurosci 24: 4469-4477, 2004.
35. Bingham S, Davey PT, Babbs AJ, Irving EA, Sammons MJ, Wyles M, Jeffrey P, Cutler L, Riba I, Johns A, Porter RA, Upton N, Hunter AJ, Parsons AA. Orexin-A, an hypothalamic peptide with analgesic properties. Pain 92: 81-90, 2001.
36. Birdsall NJ. Class A GPCR heterodimers: evidence from binding studies. Trends Pharmacol Sci 31: 499-508, 2010.
37. Bisetti A, Cvetkovic V, Serafin M, Bayer L, Machard D, Jones BE, Muhlethaler M. Excitatory action of hypocretin/orexin on neurons of the central medial amygdala. Neuroscience 142: 999-1004, 2006.
38. Blanco M, Lopez M, Garcia-Caballero T, Gallego R, Vazquez-Boquete A, Morel G, Senaris R, Casanueva F, Dieguez C, Beiras A. Cellular localization of orexin receptors in human pituitary. J Clin Endocrinol Metab 86: 1616-1619, 2001.
39. Blouin AM, Thannickal TC, Worley PF, Baraban JM, Reti IM, Siegel JM. Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy. Neurology 65: 1189-1192, 2005.
40. Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49: 589-601, 2006.
41. Bourgin P, Huitron-Resendiz S, Spier AD, Fabre V, Morte B, Criado JR, Sutcliffe JG, Henriksen SJ, de Lecea L. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci 20: 7760-7765, 2000.
42. Boutrel B, Cannella N, de Lecea L. The role of hypocretin in driving arousal and goal-oriented behaviors. Brain Res 1314: 103-111, 2010.
43. Boutrel B, Kenny PJ, Specio SE, Martin-Fardon R, Markou A, Koob GF, de Lecea L. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc Natl Acad Sci USA 102: 19168-19173, 2005.
44. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, Mueller C, Nayler O, van Gerven J, de Haas SL, Hess P, Qiu C, Buchmann S, Scherz M, Weller T, Fischli W, Clozel M, Jenck F. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13: 150-155, 2007.
45. Briski KP, Sylvester PW. Hypothalamic orexin-A-immunpositive neurons express Fos in response to central glucopenia. Neuroreport 12: 531-534, 2001.
46. Broberger C, De Lecea L, Sutcliffe JG, Hokfelt T. Hypocretin/orexinand melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. J Comp Neurol 402: 460-474, 1998.
47. Brown RE, Sergeeva O, Eriksson KS, Haas HL. Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat. Neuropharmacology 40: 457-459, 2001.
48. Brunton PJ, Russell JA. Hypothalamic-pituitary-adrenal responses to centrally administered orexin-A are suppressed in pregnant rats. J Neuroendocrinol 15: 633-637, 2003.
49. + channels mediate inhibition of orexin neurons by glucose. Neuron 50: 711-722, 2006.
50. Burdakov D, Lesage F. Glucose-induced inhibition: how many ionic mechanisms? Acta Physiol (Oxf) 198: 295-301, 2010.
51. Burdakov D, Liss B, Ashcroft FM. Orexin excites GABAergic neurons of the arcuate nucleus by activating the sodium-calcium exchanger. J Neurosci 23: 4951-4957, 2003.
52. Burdyga G, Lal S, Spiller D, Jiang W, Thompson D, Attwood S, Saeed S, Grundy D, Varro A, Dimaline R, Dockray GJ. Localization of orexin-1 receptors to vagal afferent neurons in the rat and humans. Gastroenterology 124: 129-139, 2003.
53. Burlet S, Tyler CJ, Leonard CS. Direct and indirect excitation of laterodorsal tegmental neurons by hypocretin/orexin peptides: implications for wakefulness and narcolepsy. J Neurosci 22: 2862-2872, 2002.
54. Butterick TA, Nixon JP, Billington CJ, Kotz CM. Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model. Neurosci Lett 524: 30-34, 2012.
55. Cai XJ, Denis R, Vernon RG, Clapham JC, Wilson S, Arch JR, Williams G. Food restriction selectively increases hypothalamic orexin-B levels in lactating rats. Regul Pept 97: 163-168, 2001.
56. Cai XJ, Evans ML, Lister CA, Leslie RA, Arch JR, Wilson S, Williams G. Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels: responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract. Diabetes 50: 105-112, 2001.
57. Cai XJ, Widdowson PS, Harrold J, Wilson S, Buckingham RE, Arch JR, Tadayyon M, Clapham JC, Wilding J, Williams G. Hypothalamic orexin expression: modulation by blood glucose and feeding. Diabetes 48: 2132-2137, 1999.
58. Campbell RE, Grove KL, Smith MS. Gonadotropin-releasing hormone neurons coexpress orexin 1 receptor immunoreactivity and receive direct contacts by orexin fibers. Endocrinology 144: 1542-1548, 2003.
59. Campbell RE, Smith MS, Allen SE, Grayson BE, Ffrench-Mullen JM, Grove KL. Orexin neurons express a functional pancreatic polypeptide Y4 receptor. J Neurosci 23: 1487-1497, 2003.
60. Cason AM, Smith RJ, Tahsili-Fahadan P, Moorman DE, Sartor GC, Aston-Jones G. Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity. Physiol Behav 100: 419-428, 2010.
61. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98: 437-451, 1999.
62. Chen C, Xu R. The in vitro regulation of growth hormone secretion by orexins. Endocrine 22: 57-66, 2003.
63. Chen J, Karteris E, Collins D, Randeva HS. Differential expression of mouse orexin receptor type-2 (OX2R) variants in the mouse brain. Brain Res 1103: 20-24, 2006.
64. Chen J, Randeva HS. Genomic organization of mouse orexin receptors: characterization of two novel tissue-specific splice variants. Mol Endocrinol 18: 2790-2804, 2004.
65. Chen XW, Huang W, Yan JA, Fan HX, Guo N, Lu J, Xiu Y, Gu JL, Zhang CX, Ruan HZ, Hu ZA, Yu ZP, Zhou Z. Reinvestigation of the effect of orexin A on catecholamine release from adrenal chromaffin cells. Neurosci Lett 436: 181-184, 2008.
66. Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330: 1091-1095, 2010.
67. Chollet A, Turcatti G. Biophysical approaches to G protein-coupled receptors: structure, function and dynamics. J Comput Aided Mol Des 13: 209-219, 1999.
68. Chou TC, Lee CE, Lu J, Elmquist JK, Hara J, Willie JT, Beuckmann CT, Chemelli RM, Sakurai T, Yanagisawa M, Saper CB, Scammell TE. Orexin (hypocretin) neurons contain dynorphin. J Neurosci 21: RC168-RC173, 2001.
69. Coleman PJ, Renger JJ. Orexin receptor antagonists: a review of promising compounds patented since 2006. Expert Opin Ther Pat 20: 307-324, 2010.
70. Congreve M, Marshall F. The impact of GPCR structures on pharmacology and structure-based drug design. Br J Pharmacol 159: 986-996, 2010.
71. Crespo I, Gomez de Heras R, Rodriguez de Fonseca F, Navarro M. Pretreatment with subeffective doses of Rimonabant attenuates orexigenic actions of orexin A-hypocretin 1. Neuropharmacology 54: 219-225, 2008.
72. Crocker A, Espana RA, Papadopoulou M, Saper CB, Faraco J, Sakurai T, Honda M, Mignot E, Scammell TE. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology 65: 1184-1188, 2005.
73. Cvetkovic-Lopes V, Bayer L, Dorsaz S, Maret S, Pradervand S, Dauvilliers Y, Lecendreux M, Lammers GJ, Donjacour CE, Du Pasquier RA, Pfister C, Petit B, Hor H, Muhlethaler M, Tafti M. Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. J Clin Invest 120: 713-719, 2010.
74. Darker JG, Porter RA, Eggleston DS, Smart D, Brough SJ, Sabido-David C, Jerman JC. Structure-activity analysis of truncated orexin-A analogues at the orexin-1 receptor. Bioorg Med Chem Lett 11: 737-740, 2001.
75. Date Y, Mondal MS, Matsukura S, Ueta Y, Yamashita H, Kaiya H, Kangawa K, Nakazato M. Distribution of orexin/hypocretin in the rat median eminence and pituitary. Brain Res Mol Brain Res 76: 1-6, 2000.
76. Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci USA 96: 748-753, 1999.
77. Davis SF, Williams KW, Xu W, Glatzer NR, Smith BN. Selective enhancement of synaptic inhibition by hypocretin (orexin) in rat vagal motor neurons: implications for autonomic regulation. J Neurosci 23: 3844-3854, 2003.
78. De Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95: 322-327, 1998.
79. de Oliveira CV, Rosas-Arellano MP, Solano-Flores LP, Ciriello J. Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 284: H1369-H1377, 2003.
80. Dennis EA, Cao J, Hsu YH, Magrioti V, Kokotos G. Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem Rev 111: 6130-6185, 2011.
81. Diano S, Horvath B, Urbanski HF, Sotonyi P, Horvath TL. Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. Endocrinology 144: 3774-3778, 2003.
82. Digby JE, Chen J, Tang JY, Lehnert H, Matthews RN, Randeva HS. Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B. J Endocrinol 191: 129-136, 2006.
83. + conductances contribute to resting membrane potential and to orexin-induced membrane depolarization in rat thalamic paraventricular nucleus neurons. Neuroscience 158: 1560-1570, 2009.
84. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer 7: 79-94, 2007.
85. Dube MG, Kalra SP, Kalra PS. Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action. Brain Res 842: 473-477, 1999.
86. Dugovic C, Shelton JE, Aluisio LE, Fraser IC, Jiang X, Sutton SW, Bonaventure P, Yun S, Li X, Lord B, Dvorak CA, Carruthers NI, Lovenberg TW. Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat. J Pharmacol Exp Ther 330: 142-151, 2009.
87. Duguay D, Belanger-Nelson E, Mongrain V, Beben A, Khatchadourian A, Cermakian N. Dynein light chain Tctex-type 1 modulates orexin signaling through its interaction with orexin 1 receptor. PLos One 6: e26430, 2011.
88. Eggermann E, Serafin M, Bayer L, Machard D, Saint-Mleux B, Jones BE, Muhlethaler M. Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience 108: 177-181, 2001.
89. Ehrstrom M, Gustafsson T, Finn A, Kirchgessner A, Gryback P, Jacobsson H, Hellstrom PM, Naslund E. Inhibitory effect of exogenous orexin a on gastric emptying, plasma leptin, and the distribution of orexin and orexin receptors in the gut and pancreas in man. J Clin Endocrinol Metab 90: 2370-2377, 2005.
90. 2+ influx and ERK. Biochem Biophys Res Commun 353: 475-480, 2007.
91. El Firar A, Voisin T, Rouyer-Fessard C, Ostuni MA, Couvineau A, Laburthe M. Discovery of a functional immunoreceptor tyrosine-based switch motif in a 7-transmembrane-spanning receptor: role in the orexin receptor OX1R-driven apoptosis. FASEB J 23: 4069-4080, 2009.
92. Elias CF, Saper CB, Maratos-Flier E, Tritos NA, Lee C, Kelly J, Tatro JB, Hoffman GE, Ollmann MM, Barsh GS, Sakurai T, Yanagisawa M, Elmquist JK. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402: 442-459, 1998.
93. Ellis J, Pediani JD, Canals M, Milasta S, Milligan G. Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function. J Biol Chem 281: 38812-38824, 2006.
94. Eriksson KS, Sergeeva O, Brown RE, Haas HL. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J Neurosci 21: 9273-9279, 2001.
95. Eriksson KS, Sergeeva OA, Selbach O, Haas HL. Orexin (hypocretin)/ dynorphin neurons control GABAergic inputs to tuberomammillary neurons. Eur J Neurosci 19: 1278-1284, 2004.
96. Evans NA, Groarke DA, Warrack J, Greenwood CJ, Dodgson K, Milligan G, Wilson S. Visualizing differences in ligand-induced betaarrestin- GFP interactions and trafficking between three recently characterized G protein-coupled receptors. J Neurochem 77: 476-485, 2001.
97. Fadel J, Deutch AY. Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 111: 379-387, 2002.
98. Fanelli F, De Benedetti PG. Update 1 of: computational modeling approaches to structure-function analysis of G protein-coupled receptors. Chem Rev 111: PR438-535, 2011.
99. Faraco JH, Appelbaum L, Marin W, Gaus SE, Mourrain P, Mignot E. Regulation of hypocretin (orexin) expression in embryonic zebrafish. J Biol Chem 281: 29753-29761, 2006.
100. Flemstrom G, Bengtsson MW, Makela K, Herzig KH. Effects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagogues. Acta Physiol (Oxf) 198: 373-380, 2010.
101. Flemström G, Sjöblom M, Jedstedt G, Åkerman KE. Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin. Am J Physiol Gastrointest Liver Physiol 285: G1091-G1096, 2003.
102. Florenzano F, Viscomi MT, Mercaldo V, Longone P, Bernardi G, Bagni C, Molinari M, Carrive P. P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons. J Comp Neurol 498: 58-67, 2006.
103. Follwell MJ, Ferguson AV. Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus. J Physiol 545: 855-867, 2002.
104. Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL. Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss? Brain 133: 1300-1311, 2010.
105. Fronczek R, Lammers GJ, Balesar R, Unmehopa UA, Swaab DF. The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome. J Clin Endocrinol Metab 90: 5466-5470, 2005.
106. Fronczek R, Overeem S, Lee SY, Hegeman IM, van Pelt J, van Duinen SG, Lammers GJ, Swaab DF. Hypocretin (orexin) loss in Parkinson's disease. Brain 130: 1577-1585, 2007.
107. Fronczek R, Overeem S, Reijntjes R, Lammers GJ, van Dijk JG, Pijl H. Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy. J Clin Sleep Med 4: 248-254, 2008.
108. Fu LY, Acuna-Goycolea C, van den Pol AN. Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms: tonic depression of the hypothalamic arousal system. J Neurosci 24: 8741-8751, 2004.
109. Fujiki N, Yoshida Y, Ripley B, Mignot E, Nishino S. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin- ligand-deficient narcoleptic dog. Sleep 26: 953-959, 2003.
110. Fujiki N, Yoshida Y, Zhang S, Sakurai T, Yanagisawa M, Nishino S. Sex difference in body weight gain and leptin signaling in hypocretin/ orexin deficient mouse models. Peptides 27: 2326-2331, 2006.
111. Funahashi H, Yamada S, Kageyama H, Takenoya F, Guan JL, Shioda S. Co-existence of leptin- and orexin-receptors in feedingregulating neurons in the hypothalamic arcuate nucleus-a triple labeling study. Peptides 24: 687-694, 2003.
112. Funato H, Tsai AL, Willie JT, Kisanuki Y, Williams SC, Sakurai T, Yanagisawa M. Enhanced orexin receptor-2 signaling prevents dietinduced obesity and improves leptin sensitivity. Cell Metab 9: 64-76, 2009.
113. Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137: 29-36, 2006.
114. Gerashchenko D, Horvath TL, Xie XS. Direct inhibition of hypocretin/ orexin neurons in the lateral hypothalamus by nociceptin/orphanin FQ blocks stress-induced analgesia in rats. Neuropharmacology 60: 543-549, 2011.
115. Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 21: 7273-7283, 2001.
116. Gonzalez JA, Horjales-Araujo E, Fugger L, Broberger C, Burdakov D. Stimulation of orexin/hypocretin neurones by thyrotropin-releasing hormone. J Physiol 587: 1179-1186, 2009.
117. Govindaiah G, Cox CL. Modulation of thalamic neuron excitability by orexins. Neuropharmacology 51: 414-425, 2006.
118. Grabauskas G, Moises HC. Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin. J Physiol 549: 37-56, 2003.
119. Greco MA, Shiromani PJ. Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats. Brain Res Mol Brain Res 88: 176-182, 2001.
120. Griffond B, Deray A, Fellmann D, Ciofi P, Croix D, Bugnon C. Colocalization of prolactin- and dynorphin-like substances in a neuronal population of the rat lateral hypothalamus. Neurosci Lett 156: 91-95, 1993.
121. Griffond B, Grillon S, Duval J, Colard C, Jacquemard C, Deray A, Fellmann D. Occurrence of secretogranin II in the prolactin-immunoreactive neurons of the rat lateral hypothalamus: an in situ hybridization and immunocytochemical study. J Chem Neuroanat 9: 113-119, 1995.
122. Guan JL, Saotome T, Wang QP, Funahashi H, Hori T, Tanaka S, Shioda S. Orexinergic innervation of POMC-containing neurons in the rat arcuate nucleus. Neuroreport 12: 547-551, 2001.
123. Gudermann T, Grosse R, Schultz G. Contribution of receptor/G protein signaling to cell growth and transformation. Naunyn Schmiedebergs Arch Pharmacol 361: 345-362, 2000.
124. Gutkind JS. Regulation of mitogen-activated protein kinase signaling networks by G protein-coupled receptors. Sci STKE 2000: RE1, 2000.
125. + channels. J Neurosci 29: 2528-2533, 2009.
126. Göncz E, Strowski MZ, Grotzinger C, Nowak KW, Kaczmarek P, Sassek M, Mergler S, El-Zayat BF, Theodoropoulou M, Stalla GK, Wiedenmann B, Plockinger U. Orexin-A inhibits glucagon secretion and gene expression through a Foxo1-dependent pathway. Endocrinology 149: 1618-1626, 2008.
127. Haas HL, Lin JS. Waking with the hypothalamus. Pflügers Arch 463: 31-42, 2012.
128. Haga K, Kruse AC, Asada H, Yurugi-Kobayashi T, Shiroishi M, Zhang C, Weis WI, Okada T, Kobilka BK, Haga T, Kobayashi T. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482: 547-551, 2012.
129. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI, Piper DC, Hunter AJ, Porter RA, Upton N. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci USA 96: 10911-10916, 1999.
130. Haj-Dahmane S, Shen RY. The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci 25: 896-905, 2005.
131. Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, Sakurai T. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30: 345-354, 2001.
132. Hara J, Yanagisawa M, Sakurai T. Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neurosci Lett 380: 239-242, 2005.
133. Harris DM, Go VL, Reeve JR Jr, Wu SV. Stimulation of amylase release by Orexin is mediated by Orexin 2 receptor in AR42J cells. Pancreas 25: 405-410, 2002.
134. Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437: 556-559, 2005.
135. Heifetz A, Morris GB, Biggin PC, Barker O, Fryatt T, Bentley J, Hallett D, Manikowski D, Pal S, Reifegerste R, Slack M, Law R. Study of human Orexin-1 and -2 G-protein-coupled receptors with novel and published antagonists by modeling, molecular dynamics simulations, and site-directed mutagenesis. Biochemistry 51: 3178-3197, 2012.
136. Heinonen MV, Purhonen AK, Makela KA, Herzig KH. Functions of orexins in peripheral tissues. Acta Physiol (Oxf) 192: 471-485, 2008.
137. Henny P, Jones BE. Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteins. J Comp Neurol 499: 645-661, 2006.
138. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y. Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90: 291-366, 2010.
139. Hilairet S, Bouaboula M, Carriere D, Le Fur G, Casellas P. Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 278: 23731-23737, 2003.
140. Hirose M, Egashira S, Goto Y, Hashihayata T, Ohtake N, Iwaasa H, Hata M, Fukami T, Kanatani A, Yamada K. N-acyl 6,7-dimethoxy- 1,2,3,4-tetrahydroisoquinoline: the first orexin-2 receptor selective nonpeptidic antagonist. Bioorg Med Chem Lett 13: 4497-4499, 2003.
141. Hirota K, Kushikata T, Kudo M, Kudo T, Smart D, Matsuki A. Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats. Brain Res 981: 143-150, 2003.
142. Ho YC, Lee HJ, Tung LW, Liao YY, Fu SY, Teng SF, Liao HT, Mackie K, Chiou LC. Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J Neurosci 31: 14600-14610, 2011.
143. Hoang QV, Bajic D, Yanagisawa M, Nakajima S, Nakajima Y. Effects of orexin (hypocretin) on GIRK channels. J Neurophysiol 90: 693-702, 2003.
144. + channels in cultured nucleus basalis neurons. J Neurophysiol 92: 3183-3191, 2004.
145. Hoch M, Hoever P, Alessi F, Marjason J, Dingemanse J. Pharmacokinetics and tolerability of almorexant in Japanese and Caucasian healthy male subjects. Pharmacology 88: 121-126, 2011.
146. Hoch M, Hoever P, Zisowsky J, Priestley A, Fleet D, Dingemanse J. Absolute oral bioavailability of almorexant, a dual orexin receptor antagonist, in healthy human subjects. Pharmacology 89: 53-57, 2012.
147. Hoever P, de Haas SL, Dorffner G, Chiossi E, van Gerven JM, Dingemanse J. Orexin receptor antagonism: an ascending multiple-dose study with almorexant. J Psychopharmacol 26: 1071-1080, 2012.
148. Hoever P, Dorffner G, Benes H, Penzel T, Danker-Hopfe H, Barbanoj MJ, Pillar G, Saletu B, Polo O, Kunz D, Zeitlhofer J, Berg S, Partinen M, Bassetti CL, Hogl B, Ebrahim IO, Holsboer-Trachsler E, Bengtsson H, Peker Y, Hemmeter UM, Chiossi E, Hajak G, Dingemanse J. Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial. Clin Pharmacol Ther 91: 975-985, 2012.
149. Holmqvist T, Johansson L, Östman M, Ammoun S, Åkerman KE, Kukkonen JP. OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms. J Biol Chem 280: 6570-6579, 2005.
150. Holmqvist T, Åkerman KEO, Kukkonen JP. High specificity of human orexin receptors for orexins over neuropeptide Y and other neuropeptides. Neurosci Lett 305: 177-180, 2001.
151. Holmqvist T,A °kerman KEO, Kukkonen JP. Orexin signaling in recombinant neuron-like cells. FEBS Lett 526: 11-14, 2002.
152. Hondo M, Furutani N, Yamasaki M, Watanabe M, Sakurai T. Orexin neurons receive glycinergic innervations. PLos One 6: e25076, 2011.
153. Hondo M, Nagai K, Ohno K, Kisanuki Y, Willie JT, Watanabe T, Yanagisawa M, Sakurai T. Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/ wake states. Acta Physiol (Oxf) 198: 287-294, 2010.
154. Horvath TL, Diano S, van den Pol AN. Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: a novel circuit implicated in metabolic and endocrine regulations. J Neurosci 19: 1072-1087, 1999.
155. Horvath TL, Peyron C, Diano S, Ivanov A, Aston-Jones G, Kilduff TS, van Den Pol AN. Hypocretin (orexin) activation and synaptic innervation of the locus coeruleus noradrenergic system. J Comp Neurol 415: 145-159, 1999.
156. Howlett AC. Cannabinoid receptor signaling. Handb Exp Pharmacol 53-79, 2005.
157. Huang H, Acuna-Goycolea C, Li Y, Cheng HM, Obrietan K, van den Pol AN. Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. J Neurosci 27: 4870-4881, 2007.
158. Huang H, Ghosh P, van den Pol AN. Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal. J Neurophysiol 95: 1656-1668, 2006.
159. Hungs M, Fan J, Lin L, Lin X, Maki RA, Mignot E. Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines. Genome Res 11: 531-539, 2001.
160. Hwang LL, Chen CT, Dun NJ. Mechanisms of orexin-induced depolarizations in rat dorsal motor nucleus of vagus neurones in vitro. J Physiol 537: 511-520, 2001.
161. Håkansson M, de Lecea L, Sutcliffe JG, Yanagisawa M, Meister B. Leptin receptor- and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. J Neuroendocrinol 11: 653-663, 1999.
162. Ichinose M, Asai M, Sawada M, Sasaki K, Oomura Y. Induction of outward current by orexin-B in mouse peritoneal macrophages. FEBS Lett 440: 51-54, 1998.
163. Iqbal J, Pompolo S, Murakami T, Grouzmann E, Sakurai T, Meister B, Clarke IJ. Immunohistochemical characterization of localization of long-form leptin receptor (OB-Rb) in neurochemically defined cells in the ovine hypothalamus. Brain Res 920: 55-64, 2001.
164. Ishibashi M, Takano S, Yanagida H, Takatsuna M, Nakajima K, Oomura Y, Wayner MJ, Sasaki K. Effects of orexins/hypocretins on neuronal activity in the paraventricular nucleus of the thalamus in rats in vitro. Peptides 26: 471-481, 2005.
165. Ishii Y, Blundell JE, Halford JC, Upton N, Porter R, Johns A, Rodgers RJ. Satiety enhancement by selective orexin-1 receptor antagonist SB-334867: influence of test context and profile comparison with CCK-8S. Behav Brain Res 160: 11-24, 2005.
166. 2+ exchange inhibitors. Mol Cell Biochem 259: 157-161, 2004.
167. Ivanov A, Aston-Jones G. Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons. Neuroreport 11: 1755-1758, 2000.
168. Johansson L, Ekholm ME, Kukkonen JP. Multiple phospholipase activation by OX(1) orexin/hypocretin receptors. Cell Mol Life Sci 65: 1948-1956, 2008.
169. 2+ influx. Br J Pharmacol 150: 97-104, 2007.
170. Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S, Traskman-Bendz L, Goddard AW, Brundin L, Shekhar A. A key role for orexin in panic anxiety. Nat Med 16: 111-115, 2010.
171. Jäntti MH, Putula J, Somerharju P, Frohman MA, Kukkonen JP. OX1 orexin/hypocretin receptor activation of phospholipase D. Br J Pharmacol 165: 1109-1123, 2012.
172. Jöhren O, Neidert SJ, Kummer M, Dendorfer A, Dominiak P. Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 142: 3324-3331, 2001.
173. Kalatskaya I, Schussler S, Blaukat A, Muller-Esterl W, Jochum M, Proud D, Faussner A. Mutation of tyrosine in the conserved NPXXY sequence leads to constitutive phosphorylation and internalization, but not signaling, of the human B2 bradykinin receptor. J Biol Chem 279: 31268-31276, 2004.
174. Kalogiannis M, Hsu E, Willie JT, Chemelli RM, Kisanuki YY, Yanagisawa M, Leonard CS. Cholinergic modulation of narcoleptic attacks in double orexin receptor knockout mice. PLos One 6: e18697, 2011.
175. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89: 309-380, 2009.
176. Karnani M, Burdakov D. Multiple hypothalamic circuits sense and regulate glucose levels. Am J Physiol Regul Integr Comp Physiol 300: R47-R55, 2011.
177. Karnani MM, Apergis-Schoute J, Adamantidis A, Jensen LT, de Lecea L, Fugger L, Burdakov D. Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron 72: 616-629, 2011.
178. Karnani MM, Venner A, Jensen LT, Fugger L, Burdakov D. Direct and indirect control of orexin/hypocretin neurons by glycine receptors. J Physiol 589: 639-651, 2011.
179. Karteris E, Chen J, Randeva HS. Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system. J Clin Endocrinol Metab 89: 1957-1962, 2004.
180. Karteris E, Machado RJ, Chen J, Zervou S, Hillhouse EW, Randeva HS. Food deprivation differentially modulates orexin receptor expression and signalling in the rat hypothalamus and adrenal cortex. Am J Physiol Endocrinol Metab 288: E1089-E1100, 2005.
181. Karteris E, Randeva HS, Grammatopoulos DK, Jaffe RB, Hillhouse EW. Expression and coupling characteristics of the crh and orexin type 2 receptors in human fetal adrenals. J Clin Endocrinol Metab 86: 4512-4519, 2001.
182. Kaslin J, Nystedt JM, Ostergard M, Peitsaro N, Panula P. The orexin/hypocretin system in zebrafish is connected to the aminergic and cholinergic systems. J Neurosci 24: 2678-2689, 2004.
183. Kastin AJ, Akerstrom V. Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. J Pharmacol Exp Ther 289: 219-223, 1999.
184. Katayama Y, Homma T, Honda K, Hirai K. Actions of orexin-A in the myenteric plexus of the guinea-pig small intestine. Neuroreport 14: 1515-1518, 2003.
185. Kenakin T. Agonist-receptor efficacy. II. Agonist trafficking of receptor signals. Trends Pharmacol Sci 16: 232-238, 1995.
186. Kenakin T. Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther 336: 296-302, 2011.
187. Kenakin T. Ligand-selective receptor conformations revisited: the promise and the problem. Trends Pharmacol Sci 24: 346-354, 2003.
188. Kim HY, Hong E, Kim JI, Lee W. Solution structure of human orexin-A: regulator of appetite and wakefulness. J Biochem Mol Biol 37: 565-573, 2004.
189. Kim J, Nakajima K, Oomura Y, Wayner MJ, Sasaki K. Orexin-A and ghrelin depolarize the same pedunculopontine tegmental neurons in rats: an in vitro study. Peptides 30: 1328-1335, 2009.
190. Kirchgessner AL. Orexins in the brain-gut axis. Endocr Rev 23: 1-15, 2002.
191. Kirchgessner AL, Liu M. Orexin synthesis and response in the gut. Neuron 24: 941-951, 1999.
192. Kohlmeier KA, Inoue T, Leonard CS. Hypocretin/orexin peptide signalling in the ascending arousal system: elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum. J Neurophysiol 92: 221-235, 2004.
193. 2+ transients mediated by L-type calcium channels. J Neurophysiol 100: 2265-2281, 2008.
194. Kok SW, Roelfsema F, Overeem S, Lammers GJ, Strijers RL, Frolich M, Meinders AE, Pijl H. Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker. J Clin Endocrinol Metab 87: 5085-5091, 2002.
195. Kolaj M, Coderre E, Renaud LP. Orexin peptides enhance median preoptic nucleus neuronal excitability via postsynaptic membrane depolarization and enhancement of glutamatergic afferents. Neuroscience 155: 1212-1220, 2008.
196. Korotkova TM, Eriksson KS, Haas HL, Brown RE. Selective excitation of GABAergic neurons in the substantia nigra of the rat by orexin/ hypocretin in vitro. Regul Pept 104: 83-89, 2002.
197. 34+ hematopoietic stem and progenitor cells in chronic myelogenous leukemia. Oncogene 24: 5313-5324, 2005.
198. Kukkonen JP. A ménage a' trois made in heaven: G-protein-coupled receptors, lipids and TRP channels. Cell Calcium 50: 9-26, 2011.
199. Kukkonen JP. Recent progress in orexin/hypocretin physiology and pharmacology. Biomol Concepts 3: 447-463, 2012.
200. Kukkonen JP. Regulation of receptor-coupling to (multiple) G-proteins. A challenge for basic research and drug discovery. Receptors Channels 10: 167-183, 2004.
201. Kukkonen JP, Holmqvist T, Ammoun S, Åkerman KE. Functions of the orexinergic/hypocretinergic system. Am J Physiol Cell Physiol 283: C1567-C1591, 2002.
202. Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya I, Yamashita H. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 11: 1977-1980, 2000.
203. Kuwaki T. Orexin links emotional stress to autonomic functions. Auton Neurosci 161: 20-27, 2011.
204. Lambe EK, Aghajanian GK. Hypocretin (orexin) induces calcium transients in single spines postsynaptic to identified thalamocortical boutons in prefrontal slice. Neuron 40: 139-150, 2003.
205. Lang M, Bufe B, De Pol S, Reiser O, Meyerhof W, Beck-Sickinger AG. Structural properties of orexins for activation of their receptors. J Pept Sci 12: 258-266, 2006.
206. Lang M, Soll RM, Durrenberger F, Dautzenberg FM, Beck-Sickinger AG. Structure-activity studies of orexin A and orexin B at the human orexin 1 and orexin 2 receptors led to orexin 2 receptor selective and orexin 1 receptor preferring ligands. J Med Chem 47: 1153-1160, 2004.
207. Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ. Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br J Pharmacol 141: 340-346, 2004.
208. 2+ entry: evidence for involvement of trpc channels and protein kinase C regulation. J Biol Chem 280: 1771-1781, 2005.
209. Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W. Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/ orexin-B. Eur J Biochem 266: 831-839, 1999.
210. Leinninger GM, Jo YH, Leshan RL, Louis GW, Yang H, Barrera JG, Wilson H, Opland DM, Faouzi MA, Gong Y, Jones JC, Rhodes CJ, Chua S Jr, Diano S, Horvath TL, Seeley RJ, Becker JB, Munzberg H, Myers MG Jr. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab 10: 89-98, 2009.
211. Leinninger GM, Opland DM, Jo YH, Faouzi M, Christensen L, Cappellucci LA, Rhodes CJ, Gnegy ME, Becker JB, Pothos EN, Seasholtz AF, Thompson RC, Myers MG Jr. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab 14: 313-323, 2011.
212. Li Y, Gao XB, Sakurai T, van den Pol AN. Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 36: 1169-1181, 2002.
213. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ. Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology (Berl) 212: 251-265, 2010.
214. Li Y, van den Pol AN. Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. J Neurosci 26: 13037-13047, 2006.
215. Li Y, van den Pol AN. Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons. J Neurosci 25: 173-183, 2005.
216. Li Y, van den Pol AN. Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin arousal system. J Neurosci 28: 2814-2819, 2008.
217. Lin JS, Anaclet C, Sergeeva OA, Haas HL. The waking brain: an update. Cell Mol Life Sci 68: 2499-2512, 2011.
218. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98: 365-376, 1999.
219. Liu M, Blanco-Centurion C, Konadhode R, Begum S, Pelluru D, Gerashchenko D, Sakurai T, Yanagisawa M, van den Pol AN, Shiromani PJ. Orexin gene transfer into zona incerta neurons suppresses muscle paralysis in narcoleptic mice. J Neurosci 31: 6028-6040, 2011.
220. Liu RJ, van den Pol AN, Aghajanian GK. Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. J Neurosci 22: 9453-9464, 2002.
221. Lopez M, Senaris R, Gallego R, Garcia-Caballero T, Lago F, Seoane L, Casanueva F, Dieguez C. Orexin receptors are expressed in the adrenal medulla of the rat. Endocrinology 140: 5991-5994, 1999.
222. Lopez M, Seoane L, Garcia MC, Lago F, Casanueva FF, Senaris R, Dieguez C. Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus. Biochem Biophys Res Commun 269: 41-45, 2000.
223. Louhivuori LM, Jansson L, Nordstrom T, Bart G, Nasman J, Akerman KE. Selective interference with TRPC3/6 channels disrupts OX1 receptor signalling via NCX and reveals a distinct calcium influx pathway. Cell Calcium 48: 114-123, 2010.
224. Louis GW, Leinninger GM, Rhodes CJ, Myers MG Jr. Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons. J Neurosci 30: 11278-11287, 2010.
225. Lu XY, Bagnol D, Burke S, Akil H, Watson SJ. Differential distribution and regulation of OX1 and OX2 orexin/hypocretin receptor messenger RNA in the brain upon fasting. Horm Behav 37: 335-344, 2000.
226. Luberto C, Hannun YA. Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C? J Biol Chem 273: 14550-14559, 1998.
227. Lubkin M, Stricker-Krongrad A. Independent feeding and metabolic actions of orexins in mice. Biochem Biophys Res Commun 253: 241-245, 1998.
228. 2+ influx pathway necessary for coupling to phospholipase C. J Biol Chem 275: 30806-30812, 2000.
229. Luscher C, Slesinger PA. Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci 11: 301-315, 2010.
230. Mackie K, Lai Y, Westenbroek R, Mitchell R. Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15: 6552-6561, 1995.
231. 2+ signalling by the orexin receptor type 1. Biochem Pharmacol 71: 827-836, 2006.
232. Malendowicz LK, Hochol A, Ziolkowska A, Nowak M, Gottardo L, Nussdorfer GG. Prolonged orexin administration stimulates steroidhormone secretion, acting directly on the rat adrenal gland. Int J Mol Med 7: 401-404, 2001.
233. Malendowicz LK, Jedrzejczak N, Belloni AS, Trejter M, Hochol A, Nussdorfer GG. Effects of orexins A and B on the secretory and proliferative activity of immature and regenerating rat adrenal glands. Histol Histopathol 16: 713-717, 2001.
234. Malendowicz LK, Tortorella C, Nussdorfer GG. Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. J Steroid Biochem Mol Biol 70: 185-188, 1999.
235. Malherbe P, Borroni E, Gobbi L, Knust H, Nettekoven M, Pinard E, Roche O, Rogers-Evans M, Wettstein JG, Moreau JL. Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX2 receptor. Br J Pharmacol 156: 1326-1341, 2009.
236. Malherbe P, Borroni E, Pinard E, Wettstein JG, Knoflach F. Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists. Mol Pharmacol 76: 618-631, 2009.
237. Malherbe P, Roche O, Marcuz A, Kratzeisen C, Wettstein JG, Bissantz C. Mapping the binding pocket of dual antagonist almorexant to human orexin 1 and orexin 2 receptors: comparison with the selective OX1 (SB-674042) and OX2 (EMPA) antagonists. Mol Pharmacol 78: 81-93, 2010.
238. Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S. Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 485: 321-326, 2012.
239. Mangmool S, Kurose H. Gi/o protein-dependent and -independent actions of pertussis toxin (PTX). Toxins (Basel) 3: 884-899, 2011.
240. Maolood N, Meister B. Nociceptin/orphanin FQ peptide in hypothalamic neurones associated with the control of feeding behaviour. J Neuroendocrinol 22: 75-82, 2010.
241. Marcellino D, Carriba P, Filip M, Borgkvist A, Frankowska M, Bellido I, Tanganelli S, Muller CE, Fisone G, Lluis C, Agnati LF, Franco R, Fuxe K. Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis. Neuropharmacology 54: 815-823, 2008.
242. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 435: 6-25, 2001.
243. Matsuki T, Nomiyama M, Takahira H, Hirashima N, Kunita S, Takahashi S, Yagami K, Kilduff TS, Bettler B, Yanagisawa M, Sakurai T. Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc Natl Acad Sci USA 106: 4459-4464, 2009.
244. Matsuo K, Kaibara M, Uezono Y, Hayashi H, Taniyama K, Nakane Y. Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum. Eur J Pharmacol 452: 105-109, 2002.
245. Mazzocchi G, Malendowicz LK, Aragona F, Rebuffat P, Gottardo L, Nussdorfer GG. Human pheochromocytomas express orexin receptor type 2 gene and display an in vitro secretory response to orexins A and B. J Clin Endocrinol Metab 86: 4818-4821, 2001.
246. Mazzocchi G, Malendowicz LK, Gottardo L, Aragona F, Nussdorfer GG. Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. J Clin Endocrinol Metab 86: 778-782, 2001.
247. McGregor R, Damian A, Fabbiani G, Torterolo P, Pose I, Chase M, Morales FR. Direct hypothalamic innervation of the trigeminal motor nucleus: a retrograde tracer study. Neuroscience 136: 1073-1081, 2005.
248. Meerabux J, Iwayama Y, Sakurai T, Ohba H, Toyota T, Yamada K, Nagata R, Irukayama-Tomobe Y, Shimizu H, Yoshitsugu K, Ohta K, Yoshikawa T. Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects. Biol Psychiatry 58: 401-407, 2005.
249. Mieda M, Hasegawa E, Kisanuki YY, Sinton CM, Yanagisawa M, Sakurai T. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci 31: 6518-6526, 2011.
250. Mieda M, Willie JT, Hara J, Sinton CM, Sakurai T, Yanagisawa M. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci USA 101: 4649-4654, 2004.
251. Milasta S, Evans NA, Ormiston L, Wilson S, Lefkowitz RJ, Milligan G. The sustainability of interactions between the orexin-1 receptor and beta-arrestin-2 is defined by a single C-terminal cluster of hydroxy amino acids and modulates the kinetics of ERK MAPK regulation. Biochem J 387: 573-584, 2005.
252. Mobarakeh JI, Takahashi K, Sakurada S, Nishino S, Watanabe H, Kato M, Naghdi N, Yanai K. Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice. Pain 118: 254-262, 2005.
253. Mobarakeh JI, Takahashi K, Sakurada S, Nishino S, Watanabe H, Kato M, Yanai K. Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and -2) in mice. Peptides 26: 767-777, 2005.
254. Mochizuki T, Arrigoni E, Marcus JN, Clark EL, Yamamoto M, Honer M, Borroni E, Lowell BB, Elmquist JK, Scammell TE. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc Natl Acad Sci USA 108: 4471-4476, 2011.
255. Monda M, Viggiano A, Viggiano A, Fuccio F, De Luca V. Injection of orexin A into the diagonal band of Broca induces sympathetic and hyperthermic reactions. Brain Res 1018: 265-271, 2004.
256. Mondal MS, Nakazato M, Date Y, Murakami N, Hanada R, Sakata T, Matsukura S. Characterization of orexin-A and orexin-B in the microdissected rat brain nuclei and their contents in two obese rat models. Neurosci Lett 273: 45-48, 1999.
257. Mondal MS, Nakazato M, Date Y, Murakami N, Yanagisawa M, Matsukura S. Widespread distribution of orexin in rat brain and its regulation upon fasting. Biochem Biophys Res Commun 256: 495-499, 1999.
258. Morairty SR, Revel FG, Malherbe P, Moreau JL, Valladao D, Wettstein JG, Kilduff TS, Borroni E. Dual hypocretin receptor antagonism is more effective for sleep promotion than antagonism of either receptor alone. PLos One 7: e39131, 2012.
259. Moriguchi T, Sakurai T, Nambu T, Yanagisawa M, Goto K. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neurosci Lett 264: 101-104, 1999.
260. Morrison SF, Madden CJ, Tupone D. Central control of brown adipose tissue thermogenesis. Front Endocrinol (Lausanne) 3: 5, 2012.
261. + channels in isolated locus coeruleus neurons. Neurosci Res 51: 55-65, 2005.
262. Muraki Y, Yamanaka A, Tsujino N, Kilduff TS, Goto K, Sakurai T. Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor. J Neurosci 24: 7159-7166, 2004.
263. 2+ signaling in a reciprocal manner to leptin: orexigenic neuronal pathways in the mediobasal hypothalamus. Eur J Neurosci 19: 1524-1534, 2004.
264. Nakabayashi M, Suzuki T, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Date F, Takeyama J, Darnel AD, Moriya T, Sasano H. Orexin-A expression in human peripheral tissues. Mol Cell Endocrinol 205: 43-50, 2003.
265. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K. Distribution of orexin neurons in the adult rat brain. Brain Res 827: 243-260, 1999.
266. Nanmoku T, Isobe K, Sakurai T, Yamanaka A, Takekoshi K, Kawakami Y, Goto K, Nakai T. Effects of orexin on cultured porcine adrenal medullary and cortex cells. Regul Pept 104: 125-130, 2002.
267. National Institute for Heath and Welfare (Finland). Association between Pandemrix and narcolepsy confirmed among Finnish children and adolescents. http://www.thl.fi/en_US/web/en/pressrelease?id26352 (1 Sep 2011).
268. Nishino S. Hypothalamus, hypocretins/orexin, and vigilance control. Handb Clin Neurol 99: 765-782, 2011.
269. Nishino S, Okuro M, Kotorii N, Anegawa E, Ishimaru Y, Matsumura M, Kanbayashi T. Hypocretin/orexin and narcolepsy: new basic and clinical insights. Acta Physiol (Oxf) 198: 209-222, 2010.
270. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355: 39-40, 2000.
271. Nowak KW, Mackowiak P, Switonska MM, Fabis M, Malendowicz LK. Acute orexin effects on insulin secretion in the rat: in vivo and in vitro studies. Life Sci 66: 449-454, 2000.
272. Nowak KW, Strowski MZ, Switonska MM, Kaczmarek P, Singh V, Fabis M, Mackowiak P, Nowak M, Malendowicz LK. Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes. Int J Mol Med 15: 969-972, 2005.
273. Nurmio M, Tena-Sempere M, Toppari J. Orexins and the regulation of the hypothalamic-pituitary-testicular axis. Acta Physiol (Oxf) 198: 349-354, 2010.
274. 2+ entry via diacylglycerolactivated channels in differentiated neuroblastoma cells. J Neurosci 26: 10658-10666, 2006.
275. Okumura T, Takeuchi S, Motomura W, Yamada H, Egashira Si S, Asahi S, Kanatani A, Ihara M, Kohgo Y. Requirement of intact disulfide bonds in orexin-A-induced stimulation of gastric acid secretion that is mediated by OX1 receptor activation. Biochem Biophys Res Commun 280: 976-981, 2001.
276. Olafsdottir BR, Rye DB, Scammell TE, Matheson JK, Stefansson K, Gulcher JR. Polymorphisms in hypocretin/orexin pathway genes and narcolepsy. Neurology 57: 1896-1899, 2001.
277. Oldfield BJ, Giles ME, Watson A, Anderson C, Colvill LM, McKinley MJ. The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience 110: 515-526, 2002.
278. Overeem S, Black JL 3rd, Lammers GJ. Narcolepsy: immunological aspects. Sleep Med Rev 12: 95-107, 2008.
279. Overeem S, Kok SW, Lammers GJ, Vein AA, Frolich M, Meinders AE, Roelfsema F, Pijl H. Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH-secretory events. Am J Physiol Endocrinol Metab 284: E641-E647, 2003.
280. Peltonen HM, Magga JM, Bart G, Turunen PM, Antikainen MS, Kukkonen JP, Åkerman KE. Involvement of TRPC3 channels in calcium oscillations mediated by OX1 orexin receptors. Biochem Biophys Res Commun 385: 408-412, 2009.
281. Peltonen HM, Åkerman KE, Bart G. A role for PKD1 and PKD3 activation in modulation of calcium oscillations induced by orexin receptor 1 stimulation. Biochim Biophys Acta 1803: 1206-1212, 2010.
282. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6: 991-997, 2000.
283. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18: 9996-10015, 1998.
284. Plaza-Zabala A, Martin-Garcia E, de Lecea L, Maldonado R, Berrendero F. Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior. J Neurosci 30: 2300-2310, 2010.
285. Porter RA, Chan WN, Coulton S, Johns A, Hadley MS, Widdowson K, Jerman JC, Brough SJ, Coldwell M, Smart D, Jewitt F, Jeffrey P, Austin N. 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor. Bioorg Med Chem Lett 11: 1907-1910, 2001.
286. Putula J, Kukkonen JP. Mapping of the binding sites for the OX1 orexin receptor antagonist, SB-334867, using orexin/hypocretin receptor chimaeras. Neurosci Lett 506: 111-115, 2012.
287. Putula J, Turunen PM, Johansson L, Näsman J, Ra R, Korhonen L, Kukkonen JP. Orexin/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction. FEBS Lett 585: 1368-1374, 2011.
288. Putula J, Turunen PM, Jäntti MH, Ekholm ME, Kukkonen JP. Agonist ligand discrimination by the two orexin receptors depends on the expression system. Neurosci Lett 494: 57-60, 2011.
289. Rainero I, Gallone S, Rubino E, Ponzo P, Valfre W, Binello E, Fenoglio P, Gentile S, Anoaica M, Gasparini M, Pinessi L. Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache. Headache 48: 1108-1114, 2008.
290. Rainero I, Ostacoli L, Rubino E, Gallone S, Picci LR, Fenoglio P, Negro E, Rosso C, De Martino P, De Marchi M, Furlan PM, Pinessi L. Association between major mood disorders and the hypocretin receptor 1 gene. J Affect Disord 130: 487-491, 2011.
291. Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov 9: 373-386, 2010.
292. Ramanjaneya M, Conner AC, Chen J, Kumar P, Brown JE, Johren O, Lehnert H, Stanfield PR, Randeva HS. Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B. J Endocrinol 202: 249-261, 2009.
293. Ramanjaneya M, Conner AC, Chen J, Stanfield PR, Randeva HS. Orexins stimulate steroidogenic acute regulatory protein expression through multiple signaling pathways in human adrenal H295R cells. Endocrinology 149: 4106-4115, 2008.
294. Randeva HS, Karteris E, Grammatopoulos D, Hillhouse EW. Expression of orexin-A and functional orexin type 2 receptors in the human adult adrenals: implications for adrenal function and energy homeostasis. J Clin Endocrinol Metab 86: 4808-4813, 2001.
295. Rao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of synaptic efficacy in hypocretin/orexin-containing neurons by melanin concentrating hormone in the lateral hypothalamus. J Neurosci 28: 9101-9110, 2008.
296. Rios C, Gomes I, Devi LA. mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br J Pharmacol 148: 387-395, 2006.
297. Risold PY, Griffond B, Kilduff TS, Sutcliffe JG, Fellmann D. Preprohypocretin (orexin) and prolactin-like immunoreactivity are coexpressed by neurons of the rat lateral hypothalamic area. Neurosci Lett 259: 153-156, 1999.
298. Ritter SL, Hall RA. Fine-tuning of GPCR activity by receptor-interacting proteins. Nat Rev Mol Cell Biol 10: 819-830, 2009.
299. Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, Blundell JE. Dose-response effects of orexin-A on food intake and the behavioural satiety sequence in rats. Regul Pept 96: 71-84, 2000.
300. Roecker AJ, Coleman PJ. Orexin receptor antagonists: medicinal chemistry and therapeutic potential. Curr Top Med Chem 8: 977-987, 2008.
301. Rouet-Benzineb P, Rouyer-Fessard C, Jarry A, Avondo V, Pouzet C, Yanagisawa M, Laboisse C, Laburthe M, Voisin T. Orexins acting at native OX1 receptor in colon cancer and neuroblastoma cells or at recombinant OX1 receptor suppress cell growth by inducing apoptosis. J Biol Chem 279: 45875-45886, 2004.
302. Rozenfeld R, Devi LA. Exploring a role for heteromerization in GPCR signalling specificity. Biochem J 433: 11-18, 2011.
303. Rozenfeld R, Gupta A, Gagnidze K, Lim MP, Gomes I, Lee-Ramos D, Nieto N, Devi LA. AT1R-CB1R heteromerization reveals a new mechanism for the pathogenic properties of angiotensin II. EMBO J 30: 2350-2363, 2011.
304. Sadja R, Alagem N, Reuveny E. Gating of GIRK channels: details of an intricate, membrane-delimited signaling complex. Neuron 39: 9-12, 2003.
305. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8: 171-181, 2007.
306. Sakurai T. Orexins and orexin receptors: implication in feeding behavior. Regul Pept 85: 25-30, 1999.
307. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92: 573-585, 1998.
308. Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y, Kageyama H, Kunita S, Takahashi S, Goto K, Koyama Y, Shioda S, Yanagisawa M. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron 46: 297-308, 2005.
309. Samson WK, Taylor MM. Hypocretin/orexin suppresses corticotroph responsiveness in vitro. Am J Physiol Regul Integr Comp Physiol 281: R1140-R1145, 2001.
310. Samson WK, Taylor MM, Follwell M, Ferguson AV. Orexin actions in hypothalamic paraventricular nucleus: physiological consequences and cellular correlates. Regul Pept 104: 97-103, 2002.
311. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437: 1257-1263, 2005.
312. Sasaki K, Suzuki M, Mieda M, Tsujino N, Roth B, Sakurai T. Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice. PLos One 6: e20360, 2011.
313. Savinainen JR, Saario SM, Laitinen JT. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. Acta Physiol (Oxf) 204: 267-276, 2012.
314. Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol 51: 243-266, 2011.
315. Schatzberg SJ, Cutter-Schatzberg K, Nydam D, Barrett J, Penn R, Flanders J, deLahunta A, Lin L, Mignot E. The effect of hypocretin replacement therapy in a 3-year-old Weimaraner with narcolepsy. J Vet Intern Med 18: 586-588, 2004.
316. Schone C, Cao ZF, Apergis-Schoute J, Adamantidis A, Sakurai T, Burdakov D. Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ. J Neurosci 32: 12437-12443, 2012.
317. Schone C, Venner A, Knowles D, Karnani MM, Burdakov D. Dichotomous cellular properties of mouse orexin/hypocretin neurons. J Physiol 589: 2767-2779, 2011.
318. Schutze S, Potthoff K, Machleidt T, Berkovic D, Wiegmann K, Kronke M. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown. Cell 71: 765-776, 1992.
319. Scott MM, Marcus JN, Pettersen A, Birnbaum SG, Mochizuki T, Scammell TE, Nestler EJ, Elmquist JK, Lutter M. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors. Behav Brain Res 222: 289-294, 2011.
320. Selbach O, Bohla C, Barbara A, Doreulee N, Eriksson KS, Sergeeva OA, Haas HL. Orexins/hypocretins control bistability of hippocampal long-term synaptic plasticity through co-activation of multiple kinases. Acta Physiol (Oxf) 198: 277-285, 2010.
321. Sellayah D, Bharaj P, Sikder D. Orexin is required for brown adipose tissue development, differentiation, and function. Cell Metab 14: 478-490, 2011.
322. Shah BH, Catt KJ. GPCR-mediated transactivation of RTKs in the CNS: mechanisms and consequences. Trends Neurosci 27: 48-53, 2004.
323. Shin HS, Cho HS, Sung KW, Yoon BJ. Orexin-A increases cell surface expression of AMPA receptors in the striatum. Biochem Biophys Res Commun 378: 409-413, 2009.
324. Shiuchi T, Haque MS, Okamoto S, Inoue T, Kageyama H, Lee S, Toda C, Suzuki A, Bachman ES, Kim YB, Sakurai T, Yanagisawa M, Shioda S, Imoto K, Minokoshi Y. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab 10: 466-480, 2009.
325. Silva JP, von Meyenn F, Howell J, Thorens B, Wolfrum C, Stoffel M. Regulation of adaptive behaviour during fasting by hypothalamic Foxa2. Nature 462: 646-650, 2009.
326. Singareddy R, Uhde T, Commissaris R. Differential effects of hypocretins on noise-alone versus potentiated startle responses. Physiol Behav 89: 650-655, 2006.
327. Skrzypski MTTL, Kaczmarek P, Pruszynska-Oszmalek E, Pietrzak P, Szczepankiewicz D, Kolodziejski PA, Sassek M, Arafat A, Wiedenmann B, Nowak KW, Strowski MZ. Orexin A stimulates glucose uptake, lipid accumulation and adiponectin secretion from 3T3-L1 adi-pocytes and isolated primary rat adipocytes. Diabetologia 54: 1841-1852, 2011.
328. Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, Elshourbagy NA, Ellis CE, Middlemiss DN, Brown F. Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR. Br J Pharmacol 128: 1-3, 1999.
329. Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC. SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol 132: 1179-1182, 2001.
330. Smith MI, Piper DC, Duxon MS, Upton N. Evidence implicating a role for orexin-1 receptor modulation of paradoxical sleep in the rat. Neurosci Lett 341: 256-258, 2003.
331. Smith PM, Connolly BC, Ferguson AV. Microinjection of orexin into the rat nucleus tractus solitarius causes increases in blood pressure. Brain Res 950: 261-267, 2002.
332. Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG. Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Pharmacol Rev 58: 46-57, 2006.
333. Spinazzi R, Ziolkowska A, Neri G, Nowak M, Rebuffat P, Nussdorfer GG, Andreis PG, Malendowicz LK. Orexins modulate the growth of cultured rat adrenocortical cells, acting through type 1 and type 2 receptors coupled to the MAPK p42/p44- and p38-dependent cascades. Int J Mol Med 15: 847-852, 2005.
334. Squecco R, Garella R, Luciani G, Francini F, Baccari MC. Muscular effects of orexin A on the mouse duodenum: mechanical and electrophysiological studies. J Physiol 589: 5231-5246, 2011.
335. Stanley S, Pinto S, Segal J, Perez CA, Viale A, DeFalco J, Cai X, Heisler LK, Friedman JM. Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc Natl Acad Sci USA 107: 7024-7029, 2010.
336. 34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood 104: 81-88, 2004.
337. Steiner MA, Sciarretta C, Brisbare-Roch C, Strasser DS, Studer R, Jenck F. Examining the role of endogenous orexins in hypothalamuspituitary- adrenal axis endocrine function using transient dual orexin receptor antagonism in the rat. Psychoneuroendocrinology. [Epub ahead of print]. http://dx.doi.org/10.1016/j.psyneuen.2012.07.016.
338. Sunahara RK, Taussig R. Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol Interv 2: 168-184, 2002.
339. Suzuki M, Beuckmann CT, Shikata K, Ogura H, Sawai T. Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like behavior. Brain Res 1044: 116-121, 2005.
340. Swedish Medical Products Agency. Swedish Medical Products Agency publishes report from a case inventory study on Pandemrix vaccination and development of narcolepsy with cataplexy. Euro Surveill 16: 2011.
341. Sweet DC, Levine AS, Billington CJ, Kotz CM. Feeding response to central orexins. Brain Res 821: 535-538, 1999.
342. Switonska MM, Kaczmarek P, Malendowicz LK, Nowak KW. Orexins and adipoinsular axis function in the rat. Regul Pept 104: 69-73, 2002.
343. Tafuri S, Muto RL, Pavone LM, Valiante S, Costagliola A, Staiano N, Vittoria A. Novel localization of orexin A in the tubular cytotypes of the rat testis. Regul Pept 164: 53-57, 2010.
344. Takai T, Takaya T, Nakano M, Akutsu H, Nakagawa A, Aimoto S, Nagai K, Ikegami T. Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic N-terminal region, revealing the structural basis of specific recognition by the orexin-1 receptor. J Pept Sci 12: 443-454, 2006.
345. Tam JK, Lau KW, Lee LT, Chu JY, Ng KM, Fournier A, Vaudry H, Chow BK. Origin of secretin receptor precedes the advent of tetrapoda: evidence on the separated origins of secretin and orexin. PLos One 6: e19384, 2011.
346. Tang J, Chen J, Ramanjaneya M, Punn A, Conner AC, Randeva HS. The signalling profile of recombinant human orexin-2 receptor. Cell Signal 20: 1651-1661, 2008.
347. Tapaneeyakorn S, Goddard AD, Oates J, Willis CL, Watts A. Solution- and solid-state NMR studies of GPCRs and their ligands. Biochim Biophys Acta 1808: 1462-1475, 2011.
348. 2+ signalling: problems and pitfalls. Trends Pharmacol Sci 19: 370-375, 1998.
349. Thakkar MM, Winston S, McCarley RW. Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res 944: 190-194, 2002.
350. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Reduced number of hypocretin neurons in human narcolepsy. Neuron 27: 469-474, 2000.
351. Thannickal TC, Nienhuis R, Siegel JM. Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy. Sleep 32: 993-998, 2009.
352. Thannickal TC, Siegel JM, Nienhuis R, Moore RY. Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy. Brain Pathol 13: 340-351, 2003.
353. Thompson JL, Borgland SL. A role for hypocretin/orexin in motivation. Behav Brain Res 217: 446-453, 2011.
354. Thorpe AJ, Mullett MA, Wang C, Kotz CM. Peptides that regulate food intake: regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation. Am J Physiol Regul Integr Comp Physiol 284: R1409-R1417, 2003.
355. Torrealba F, Yanagisawa M, Saper CB. Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats. Neuroscience 119: 1033-1044, 2003.
356. Tran DT, Bonaventure P, Hack M, Mirzadegan T, Dvorak C, Letavic M, Carruthers N, Lovenberg T, Sutton SW. Chimeric, mutant orexin receptors show key interactions between orexin receptors, peptides and antagonists. Eur J Pharmacol 667: 120-128, 2011.
357. Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438: 71-75, 1998.
358. Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, Takahashi S, Goto K, Sakurai T. Cholecystokinin activates orexin/ hypocretin neurons through the cholecystokinin A receptor. J Neurosci 25: 7459-7469, 2005.
359. Tsunematsu T, Fu LY, Yamanaka A, Ichiki K, Tanoue A, Sakurai T, van den Pol AN. Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis. J Neurosci 28: 228-238, 2008.
360. Tsunematsu T, Kilduff TS, Boyden ES, Takahashi S, Tominaga M, Yamanaka A. Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci 31: 10529-10539, 2011.
361. Tsunematsu T, Tanaka KF, Yamanaka A, Koizumi A. Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light. Neurosci Res. [Epub ahead of print]. http://dx.doi.org/10.1016/j.neures.2012.07.005.
362. Tupone D, Madden CJ, Cano G, Morrison SF. An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis. J Neurosci 31: 15944-15955, 2011.
363. Turunen PM, Ekholm ME, Somerharju P, Kukkonen JP. Arachidonic acid release mediated by OX1 orexin receptors. Br J Pharmacol 159: 212-221, 2010.
364. Turunen PM, Jäntti MH, Kukkonen JP. OX1 orexin/hypocretin receptor signaling via arachidonic acid and endocannabinoid release. Mol Pharmacol 82: 156-167, 2012.
365. Turunen PM, Putula J, Kukkonen JP. Filtration assay for arachidonic acid release. Anal Biochem 407: 233-236, 2010.
366. Twitchell W, Brown S, Mackie K. Cannabinoids inhibit N- and P/Qtype calcium channels in cultured rat hippocampal neurons. J Neurophysiol 78: 43-50, 1997.
367. 2+ signaling in dopamine neurons of the ventral tegmental area. Neuroreport 12: 1885-1889, 2001.
368. Van den Pol AN. Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 19: 3171-3182, 1999.
369. Van Den Pol AN, Acuna-Goycolea C, Clark KR, Ghosh PK. Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron 42: 635-652, 2004.
370. van den Pol AN, Gao XB, Obrietan K, Kilduff TS, Belousov AB. Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptide, hypocretin/orexin. J Neurosci 18: 7962-7971, 1998.
371. Van den Pol AN, Patrylo PR, Ghosh PK, Gao XB. Lateral hypothalamus: early developmental expression and response to hypocretin (orexin). J Comp Neurol 433: 349-363, 2001.
372. Van den Top M, Nolan MF, Lee K, Richardson PJ, Buijs RM, Davies CH, Spanswick D. Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones. J Physiol 549: 809-821, 2003.
373. Wang J, Osaka T, Inoue S. Energy expenditure by intracerebroventricular administration of orexin to anesthetized rats. Neurosci Lett 315: 49-52, 2001.
374. Ward RJ, Pediani JD, Milligan G. Hetero-multimerization of the cannabinoid CB1 receptor and the orexin OX1 receptor generates a unique complex in which both protomers are regulated by orexin A. J Biol Chem 286: 37414-37428, 2011.
375. Watanabe S, Kuwaki T, Yanagisawa M, Fukuda Y, Shimoyama M. Persistent pain and stress activate pain-inhibitory orexin pathways. Neuroreport 16: 5-8, 2005.
376. Watson SL, Watson CJ, Baghdoyan HA, Lydic R. Thermal nociception is decreased by hypocretin-1 and an adenosine A1 receptor agonist microinjected into the pontine reticular formation of Sprague Dawley rat. J Pain 11: 535-544, 2010.
377. Vennekens R, Voets T, Bindels RJ, Droogmans G, Nilius B. Current understanding of mammalian TRP homologues. Cell Calcium 31: 253-264, 2002.
378. Venner A, Karnani MM, Gonzalez JA, Jensen LT, Fugger L, Burdakov D. Orexin neurons as conditional glucosensors: paradoxical regulation of sugar sensing by intracellular fuels. J Physiol 589: 5701-5708, 2011.
379. Wenzel J, Grabinski N, Knopp CA, Dendorfer A, Ramanjaneya M, Randeva HS, Ehrhart-Bornstein M, Dominiak P, Johren O. Hypocretin/ orexin increases the expression of steroidogenic enzymes in human adrenocortical NCI H295R cells. Am J Physiol Regul Integr Comp Physiol 297: R1601-R1609, 2009.
380. Williams RH, Alexopoulos H, Jensen LT, Fugger L, Burdakov D. Adaptive sugar sensors in hypothalamic feeding circuits. Proc Natl Acad Sci USA 105: 11975-11980, 2008.
381. Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, Marcus JN, Lee C, Elmquist JK, Kohlmeier KA, Leonard CS, Richardson JA, Hammer RE, Yanagisawa M. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 38: 715-730, 2003.
382. Willie JT, Chemelli RM, Sinton CM, Yanagisawa M. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci 24: 429-458, 2001.
383. Winrow CJ, Gotter AL, Cox CD, Doran SM, Tannenbaum PL, Breslin MJ, Garson SL, Fox SV, Harrell CM, Stevens J, Reiss DR, Cui D, Coleman PJ, Renger JJ. Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist. J Neurogenet 25: 52-61, 2011.
384. Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci 24: 11439-11448, 2004.
385. Voisin T, El Firar A, Fasseu M, Rouyer-Fessard C, Descatoire V, Walker F, Paradis V, Bedossa P, Henin D, Lehy T, Laburthe M. Aberrant expression of OX1 receptors for orexins in colon cancers and liver metastases: an openable gate to apoptosis. Cancer Res 71: 3341-3351, 2011.
386. Voisin T, El Firar A, Rouyer-Fessard C, Gratio V, Laburthe M. A hallmark of immunoreceptor, the tyrosine-based inhibitory motif ITIM, is present in the G protein-coupled receptor OX1R for orexins and drives apoptosis: a novel mechanism. FASEB J 22: 1993-2002, 2008.
387. Voisin T, Firar AE, Avondo V, Laburthe M. Orexin-induced apoptosis: the key role of the seven-transmembrane domain orexin type 2 receptor. Endocrinology 147: 4977-4984, 2006.
388. Voisin T, Rouet-Benzineb P, Reuter N, Laburthe M. Orexins and their receptors: structural aspects and role in peripheral tissues. Cell Mol Life Sci 60: 72-87, 2003.
389. Wollmann G, Acuna-Goycolea C, van den Pol AN. Direct excitation of hypocretin/orexin cells by extracellular ATP at P2X receptors. J Neurophysiol 94: 2195-2206, 2005.
390. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330: 1066-1071, 2010.
391. Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC. Structure of the human kappa-opioid receptor in complex with JDTic. Nature 485: 327-332, 2012.
392. Wu M, Zaborszky L, Hajszan T, van den Pol AN, Alreja M. Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons. J Neurosci 24: 3527-3536, 2004.
393. Wu M, Zhang Z, Leranth C, Xu C, van den Pol AN, Alreja M. Hypocretin increases impulse flow in the septohippocampal GABAergic pathway: implications for arousal via a mechanism of hippocampal disinhibition. J Neurosci 22: 7754-7765, 2002.
394. Xia J, Chen X, Song C, Ye J, Yu Z, Hu Z. Postsynaptic excitation of prefrontal cortical pyramidal neurons by hypocretin-1/orexin A through the inhibition of potassium currents. J Neurosci Res 82: 729-736, 2005.
395. Xie LH, John SA, Ribalet B, Weiss JN. Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): interaction with other regulatory ligands. Prog Biophys Mol Biol 94: 320-335, 2007.
396. Xie X, Crowder TL, Yamanaka A, Morairty SR, Lewinter RD, Sakurai T, Kilduff TS. GABA(B) receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus. J Physiol 574: 399-414, 2006.
397. Xie X, Wisor JP, Hara J, Crowder TL, LeWinter R, Khroyan TV, Yamanaka A, Diano S, Horvath TL, Sakurai T, Toll L, Kilduff TS. Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. J Clin Invest 118: 2471-2481, 2008.
398. 2+ currents and synergistically increases growth hormone (GH) secretion with GHreleasing hormone in primary cultured ovine somatotropes. Endocrinology 143: 4609-4619, 2002.
399. Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 137: 170-176, 2002.
400. Yamamoto T, Saito O, Shono K, Aoe T, Chiba T. Anti-mechanical allodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model. Neurosci Lett 347: 183-186, 2003.
401. Yamamoto T, Saito O, Shono K, Hirasawa S. Activation of spinal orexin-1 receptor produces anti-allodynic effect in the rat carrageenan test. Eur J Pharmacol 481: 175-180, 2003.
402. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38: 701-713, 2003.
403. Yamanaka A, Muraki Y, Ichiki K, Tsujino N, Kilduff TS, Goto K, Sakurai T. Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner. J Neurophysiol 96: 284-298, 2006.
404. Yamanaka A, Tabuchi S, Tsunematsu T, Fukazawa Y, Tominaga M. Orexin directly excites orexin neurons through orexin 2 receptor. J Neurosci 30: 12642-12652, 2010.
405. Yang B, Ferguson AV. Orexin-A depolarizes dissociated rat area postrema neurons through activation of a nonselective cationic conductance. J Neurosci 22: 6303-6308, 2002.
406. + conductances. J Neurophysiol 89: 2167-2175, 2003.
407. Yang B, Samson WK, Ferguson AV. Excitatory effects of orexin-A on nucleus tractus solitarius neurons are mediated by phospholipase C and protein kinase C. J Neurosci 23: 6215-6222, 2003.
408. Yokobori E, Kojima K, Azuma M, Kang KS, Maejima S, Uchiyama M, Matsuda K. Stimulatory effect of intracerebroventricular administration of orexin A on food intake in the zebrafish, Danio rerio. Peptides 32: 1357-1362, 2011.
409. Yoshida K, McCormack S, Espana RA, Crocker A, Scammell TE. Afferents to the orexin neurons of the rat brain. J Comp Neurol 494: 845-861, 2006.
410. Zhang J, Li B, Yu L, He YC, Li HZ, Zhu JN, Wang JJ. A role for orexin in central vestibular motor control. Neuron 69: 793-804, 2011.
411. + conductances contribute to a slow AHP in thalamic paraventricular nucleus neurons: a novel target for orexin receptors. J Neurophysiol 104: 2052-2062, 2010.
412. Zhang W, Sunanaga J, Takahashi Y, Mori T, Sakurai T, Kanmura Y, Kuwaki T. Orexin neurons are indispensable for stress-induced thermogenesis in mice. J Physiol 588: 4117-4129, 2010.
413. Zheng H, Patterson LM, Berthoud HR. Orexin-A projections to the caudal medulla and orexin-induced c-Fos expression, food intake, and autonomic function. J Comp Neurol 485: 127-142, 2005.
414. Zhu Y, Miwa Y, Yamanaka A, Yada T, Shibahara M, Abe Y, Sakurai T, Goto K. Orexin receptor type-1 couples exclusively to pertussis toxin-insensitive G-proteins, while orexin receptor type-2 couples to both pertussis toxin-sensitive and -insensitive G-proteins. J Pharm Sci 92: 259-266, 2003.
415. Zwirska-Korczala K, Adamczyk-Sowa M, Sowa P, Pilc K, Suchanek R, Pierzchala K, Namyslowski G, Misiolek M, Sodowski K, Kato I, Kuwahara A, Zabielski R. Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J Physiol Pharmacol 58, Suppl 1: 53-64, 2007.