The Role of Orexin/Hypocretin in the Central Nervous System and Peripheral Tissues

Vitamins and Hormones

Volumn 89, Issue , 2012, Pages 19-33

  Tsunematsu, Tomomi ^a   Yamanaka, Akihiro ^a,b,c  

^a NATIONAL INSTITUTE FOR PHYSIOLOGICAL SCIENCES   (Japan)

^b GRADUATE UNIVERSITY FOR ADVANCED STUDIES   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

Autonomic nervous system; Feeding behavior; Hypothalamic pituitary adrenal axis; Narcolepsy; Orexin Hypocretin

Indexed keywords

EID: 84861469836     PISSN: 00836729     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-394623-2.00002-0     Document Type: Chapter

References (67)

1. Abrahamson E.E., Leak R.K., Moore R.Y. The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 2001, 12:435-440.
2. Al-Barazanji K.A., Wilson S., Baker J., Jessop D.S., Harbuz M.S. Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats. J. Neuroendocrinol. 2001, 13:421-424.
3. Arihara Z., Takahashi K., Murakami O., Totsune K., Sone M., Satoh F., Ito S., Mouri T. Immunoreactive orexin-A in human plasma. Peptides 2001, 22:139-142.
4. Boutrel B., Kenny P.J., Specio S.E., Martin-Fardon R., Markou A., Koob G.F., de Lecea L. Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:19168-19173.
5. Brunton P.J., Russell J.A. Hypothalamic-pituitary-adrenal responses to centrally administered orexin-A are suppressed in pregnant rats. J. Neuroendocrinol. 2003, 15:633-637.
6. Burdakov D., Gerasimenko O., Verkhratsky A. Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J. Neurosci. 2005, 25:2429-2433.
7. Burdakov D., Jensen L.T., Alexopoulos H., Williams R.H., Fearon I.M., O'Kelly I., Gerasimenko O., Fugger L., Verkhratsky A. Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose. Neuron 2006, 50:711-722.
8. Chemelli R.M., Willie J.T., Sinton C.M., Elmquist J.K., Scammell T., Lee C., Richardson J.A., Williams S.C., Xiong Y., Kisanuki Y., Fitch T.E., Nakazato M., et al. Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 1999, 98:437-451.
9. Chen C.T., Hwang L.L., Chang J.K., Dun N.J. Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2000, 278:R692-R697.
10. Chou T.C., Lee C.E., Lu J., Elmquist J.K., Hara J., Willie J.T., Beuckmann C.T., Chemelli R.M., Sakurai T., Yanagisawa M., Saper C.B., Scammell T.E. Orexin (hypocretin) neurons contain dynorphin. J. Neurosci. 2001, 21:RC168.
11. 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. U.S.A. 1999, 96:748-753.
12. de Lecea L., Kilduff T.S., Peyron C., Gao X., Foye P.E., Danielson P.E., Fukuhara C., Battenberg E.L., Gautvik V.T., Bartlett F.S., Frankel W.N., van den Pol A.N., et al. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:322-327.
13. Dunn-Meynell A.A., Routh V.H., Kang L., Gaspers L., Levin B.E. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Diabetes 2002, 51:2056-2065.
14. Edwards C.M., Abusnana S., Sunter D., Murphy K.G., Ghatei M.A., Bloom S.R. The effect of the orexins on food intake: Comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J. Endocrinol. 1999, 160:R7-R12.
15. Elias C.F., Aschkenasi C., Lee C., Kelly J., Ahima R.S., Bjorbaek C., Flier J.S., Saper C.B., Elmquist J.K. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 1999, 23:775-786.
16. Gallopin T., Fort P., Eggermann E., Cauli B., Luppi P.H., Rossier J., Audinat E., Muhlethaler M., Serafin M. Identification of sleep-promoting neurons in vitro. Nature 2000, 404:992-995.
17. Gonzalez J.A., Jensen L.T., Doyle S.E., Miranda-Anaya M., Menaker M., Fugger L., Bayliss D.A., Burdakov D. Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons. Eur. J. Neurosci. 2009, 30:57-64.
18. Guyon A., Tardy M.P., Rovere C., Nahon J.L., Barhanin J., Lesage F. Glucose inhibition persists in hypothalamic neurons lacking tandem-pore K+ channels. J. Neurosci. 2009, 29:2528-2533.
19. Hakansson M., de Lecea L., Sutcliffe J.G., Yanagisawa M., Meister B. Leptin receptor- and STAT3-immunoreactivities in hypocretin/orexin neurones of the lateral hypothalamus. J. Neuroendocrinol. 1999, 11:653-663.
20. Hara J., Beuckmann C.T., Nambu T., Willie J.T., Chemelli R.M., Sinton C.M., Sugiyama F., Yagami K., Goto K., Yanagisawa M., Sakurai T. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 2001, 30:345-354.
21. 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. 2005, 380:239-242.
22. Harris G.C., Wimmer M., Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature 2005, 437:556-559.
23. Haynes A.C., Jackson B., Overend P., Buckingham R.E., Wilson S., Tadayyon M., Arch J.R. Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat. Peptides 1999, 20:1099-1105.
24. Haynes A.C., Jackson B., Chapman H., Tadayyon M., Johns A., Porter R.A., Arch J.R. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul. Pept. 2000, 96:45-51.
25. Haynes A.C., Chapman H., Taylor C., Moore G.B., Cawthorne M.A., Tadayyon M., Clapham J.C., Arch J.R. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul. Pept. 2002, 104:153-159.
26. 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. 2003, 981:143-150.
27. Jaszberenyi M., Bujdoso E., Pataki I., Telegdy G. Effects of orexins on the hypothalamic-pituitary-adrenal system. J. Neuroendocrinol. 2000, 12:1174-1178.
28. Johren O., Neidert S.J., Kummer M., Dendorfer A., Dominiak P. Prepro-orexin and orexin receptor mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 2001, 142:3324-3331.
29. Kayaba Y., Nakamura A., Kasuya Y., Ohuchi T., Yanagisawa M., Komuro I., Fukuda Y., Kuwaki T. Attenuated defense response and low basal blood pressure in orexin knockout mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 285:R581-R593.
30. Kirchgessner A.L., Liu M. Orexin synthesis and response in the gut. Neuron 1999, 24:941-951.
31. Kok S.W., Roelfsema F., Overeem S., Lammers G.J., Strijers R.L., Frolich M., Meinders A.E., 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. 2002, 87:5085-5091.
32. Kunii K., Yamanaka A., Nambu T., Matsuzaki I., Goto K., Sakurai T. Orexins/hypocretins regulate drinking behaviour. Brain Res. 1999, 842:256-261.
33. Kuru M., Ueta Y., Serino R., Nakazato M., Yamamoto Y., Shibuya I., Yamashita H. Centrally administered orexin/hypocretin activates HPA axis in rats. Neuroreport 2000, 11:1977-1980.
34. Lin L., Faraco J., Li R., Kadotani H., Rogers W., Lin X., Qiu X., de Jong P.J., Nishino S., Mignot E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999, 98:365-376.
35. Lu X.Y., Bagnol D., Burke S., Akil H., Watson S.J. Differential distribution and regulation of OX1 and OX2 orexin/hypocretin receptor messenger RNA in the brain upon fasting. Horm. Behav. 2000, 37:335-344.
36. Lu J., Bjorkum A.A., Xu M., Gaus S.E., Shiromani P.J., Saper C.B. Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep. J. Neurosci. 2002, 22:4568-4576.
37. Malendowicz L.K., Hochol A., Ziolkowska A., Nowak M., Gottardo L., Nussdorfer G.G. Prolonged orexin administration stimulates steroid-hormone secretion, acting directly on the rat adrenal gland. Int. J. Mol. Med. 2001, 7:401-404.
38. Marcus J.N., Aschkenasi C.J., Lee C.E., Chemelli R.M., Saper C.B., Yanagisawa M., Elmquist J.K. Differential expression of orexin receptors 1 and 2 in the rat brain. J. Comp. Neurol. 2001, 435:6-25.
39. Mieda M., Williams S.C., Sinton C.M., Richardson J.A., Sakurai T., Yanagisawa M. Orexin neurons function in an efferent pathway of a food-entrainable circadian oscillator in eliciting food-anticipatory activity and wakefulness. J. Neurosci. 2004, 24:10493-10501.
40. 2+ signaling in a reciprocal manner to leptin: Orexigenic neuronal pathways in the mediobasal hypothalamus. Eur. J. Neurosci. 2004, 19:1524-1534.
41. Nakabayashi M., Suzuki T., Takahashi K., Totsune K., Muramatsu Y., Kaneko C., Date F., Takeyama J., Darnel A.D., Moriya T., Sasano H. Orexin-A expression in human peripheral tissues. Mol. Cell. Endocrinol. 2003, 205:43-50.
42. Nambu T., Sakurai T., Mizukami K., Hosoya Y., Yanagisawa M., Goto K. Distribution of orexin neurons in the adult rat brain. Brain Res. 1999, 827:243-260.
43. 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. 2002, 104:125-130.
44. Narita M., Nagumo Y., Hashimoto S., Khotib J., Miyatake M., Sakurai T., Yanagisawa M., Nakamachi T., Shioda S., Suzuki T. Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J. Neurosci. 2006, 26:398-405.
45. Nishino S., Ripley B., Overeem S., Lammers G.J., Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000, 355:39-40.
46. Peyron C., Tighe D.K., van den Pol A.N., de Lecea L., Heller H.C., Sutcliffe J.G., Kilduff T.S. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J. Neurosci. 1998, 18:9996-10015.
47. Peyron C., Faraco J., Rogers W., Ripley B., Overeem S., Charnay Y., Nevsimalova S., Aldrich M., Reynolds D., Albin R., Li R., Hungs M., et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. 2000, 6:991-997.
48. Reti I.M., Reddy R., Worley P.F., Baraban J.M. Selective expression of Narp, a secreted neuronal pentraxin, in orexin neurons. J. Neurochem. 2002, 82:1561-1565.
49. Risold P.Y., Griffond B., Kilduff T.S., Sutcliffe J.G., Fellmann D. Preprohypocretin (orexin) and prolactin-like immunoreactivity are coexpressed by neurons of the rat lateral hypothalamic area. Neurosci. Lett. 1999, 259:153-156.
50. Rosin D.L., Weston M.C., Sevigny C.P., Stornetta R.L., Guyenet P.G. Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2. J. Comp. Neurol. 2003, 465:593-603.
51. Russell S.H., Small C.J., Dakin C.L., Abbott C.R., Morgan D.G., Ghatei M.A., Bloom S.R. The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats. J. Neuroendocrinol. 2001, 13:561-566.
52. Sakamoto F., Yamada S., Ueta Y. Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: Possible involvement of central orexins on stress-activated central CRF neurons. Regul. Pept. 2004, 118:183-191.
53. Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., Williams S.C., Richardson J.A., Kozlowski G.P., Wilson S., Arch J.R., Buckingham R.E., et al. Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998, 92:573-585.
54. Samson W.K., Gosnell B., Chang J.K., Resch Z.T., Murphy T.C. Cardiovascular regulatory actions of the hypocretins in brain. Brain Res. 1999, 831:248-253.
55. Shirasaka T., Nakazato M., Matsukura S., Takasaki M., Kannan H. Sympathetic and cardiovascular actions of orexins in conscious rats. Am. J. Physiol. 1999, 277:R1780-R1785.
56. Shiuchi T., Haque M.S., Okamoto S., Inoue T., Kageyama H., Lee S., Toda C., Suzuki A., Bachman E.S., Kim Y.B., Sakurai T., Yanagisawa M., et al. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab. 2009, 10:466-480.
57. Spinazzi R., Rucinski M., Neri G., Malendowicz L.K., Nussdorfer G.G. Preproorexin and orexin receptors are expressed in cortisol-secreting adrenocortical adenomas, and orexins stimulate in vitro cortisol secretion and growth of tumor cells. J. Clin. Endocrinol. Metab. 2005, 90:3544-3549.
58. Thannickal T.C., Moore R.Y., Nienhuis R., Ramanathan L., Gulyani S., Aldrich M., Cornford M., Siegel J.M. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000, 27:469-474.
59. Trivedi P., Yu H., MacNeil D.J., Van der Ploeg L.H., Guan X.M. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 1998, 438:71-75.
60. Tsunematsu T., Fu L.Y., Yamanaka A., Ichiki K., Tanoue A., Sakurai T., van den Pol A.N. Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: Implications for water homeostasis. J. Neurosci. 2008, 28:228-238.
61. Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu. Rev. Neurosci. 2001, 24:429-458.
62. Willie J.T., Chemelli R.M., Sinton C.M., Tokita S., Williams S.C., Kisanuki Y.Y., Marcus J.N., Lee C., Elmquist J.K., Kohlmeier K.A., Leonard C.S., Richardson J.A., et al. Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: Molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 2003, 38:715-730.
63. Yamada H., Okumura T., Motomura W., Kobayashi Y., Kohgo Y. Inhibition of food intake by central injection of anti-orexin antibody in fasted rats. Biochem. Biophys. Res. Commun. 2000, 267:527-531.
64. Yamanaka A., Sakurai T., Katsumoto T., Yanagisawa M., Goto K. Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res. 1999, 849:248-252.
65. Yamanaka A., Kunii K., Nambu T., Tsujino N., Sakai A., Matsuzaki I., Miwa Y., Goto K., Sakurai T. Orexin-induced food intake involves neuropeptide Y pathway. Brain Res. 2000, 859:404-409.
66. Yamanaka A., Beuckmann C.T., Willie J.T., 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 2003, 38:701-713.
67. 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. Pharmacol. Sci. 2003, 92:259-266.