RFamide peptides: Structure, function, mechanisms and pharmaceutical potential

Pharmaceuticals

Volumn 4, Issue 9, 2011, Pages 1248-1280

  Findeisen, Maria ^a   Rathmann, Daniel ^a   Beck Sickinger, Annette G ^a  

^a UNIVERSITY OF LEIPZIG   (Germany)

Author keywords

Kisspeptin; Neuropeptide FF; Prolactin releasing peptide; QRFP; RFamide

Indexed keywords

ARGINYLPHENYLALANINAMIDE; G PROTEIN COUPLED RECEPTOR 54; GONADOTROPIN; GONADOTROPIN INHIBITORY HORMONE; KISSPEPTIN; METASTIN; NEUROPEPTIDE; NEUROPEPTIDE FF; NEUROPEPTIDE FF RECEPTOR 1; NEUROPEPTIDE FF RECEPTOR 2; NEUROPEPTIDE RECEPTOR; PROLACTIN RELEASING FACTOR; PYROGLUTAMYLATED RFAMIDE PEPTIDE RECEPTOR; RECEPTOR PROTEIN; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; BIOLOGICAL ACTIVITY; CARBOXY TERMINAL SEQUENCE; DRUG BINDING; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RESEARCH; DRUG TARGETING; ENDOMETRIOSIS; GENITAL SYSTEM DISEASE; HUMAN; HYPERALGESIA; LIGAND BINDING; METASTASIS; MOLECULAR INTERACTION; NONHUMAN; PHYSIOLOGICAL PROCESS; PRECOCIOUS PUBERTY; PROSTATE CANCER; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN MOTIF; RECEPTOR AFFINITY; REVIEW; SIGNAL TRANSDUCTION; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION;

EID: 80053587990     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph4091248     Document Type: Review

References (169)

1. Price, D.A.; Greenberg, M.J. Structure of a molluscan cardioexcitatory neuropeptide. Science 1977, 197, 670-671.
2. Dockray, G.J.; Reeve, J.R., Jr.; Shively, J.; Gayton, R.J.; Barnard, C.S. A novel active pentapeptide from chicken brain identified by antibodies to FMRFamide. Nature 1983, 305, 328-330.
3. Yang, H.Y.; Fratta, W.; Majane, E.A.; Costa, E. Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine. Proc. Natl. Acad. Sci. USA 1985, 82, 7757-7761.
4. Panula, P.; Aarnisalo, A.A.; Wasowicz, K. Neuropeptide FF, a mammalian neuropeptide with multiple functions. Prog. Neurobiol. 1996, 48, 461-487.
5. Perry, S.J.; Yi-Kung Huang, E.; Cronk, D.; Bagust, J.; Sharma, R.; Walker, R.J.; Wilson, S.; Burke, J.F. A human gene encoding morphine modulating peptides related to NPFF and FMRFamide. FEBS Lett. 1997, 409, 426-430.
6. Ubuka, T.; Morgan, K.; Pawson, A.J.; Osugi, T.; Chowdhury, V.S.; Minakata, H.; Tsutsui, K.; Millar, R.P.; Bentley, G.E. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS One 2009, 4, e8400.
7. Bruzzone, F.; Lectez, B.; Tollemer, H.; Leprince, J.; Dujardin, C.; Rachidi, W.; Chatenet, D.; Baroncini, M.; Beauvillain, J.C.; Vallarino, M.; et al. Anatomical distribution and biochemical characterization of the novel RFamide peptide 26RFa in the human hypothalamus and spinal cord. J. Neurochem. 2006, 99, 616-627.
8. Hinuma, S.; Habata, Y.; Fujii, R.; Kawamata, Y.; Hosoya, M.; Fukusumi, S.; Kitada, C.; Masuo, Y.; Asano, T.; Matsumoto, H.; et al. A prolactin-releasing peptide in the brain. Nature 1998, 393, 272-276.
9. Langmead, C.J.; Szekeres, P.G.; Chambers, J.K.; Ratcliffe, S.J.; Jones, D.N.; Hirst, W.D.; Price, G.W.; Herdon, H.J. Characterization of the binding of [(125)I]-human prolactin releasing peptide (PrRP) to GPR10, a novel G protein coupled receptor. Br. J. Pharmacol. 2000, 131, 683-688.
10. Kotani, M.; Detheux, M.; Vandenbogaerde, A.; Communi, D.; Vanderwinden, J.M.; Le Poul, E.; Brezillon, S.; Tyldesley, R.; Suarez-Huerta, N.; Vandeput, F.; et al. The metastasis suppressor gene KISS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem. 2001, 276, 34631-34636.
11. Lee, J.H.; Miele, M.E.; Hicks, D.J.; Phillips, K.K.; Trent, J.M.; Weissman, B.E.; Welch, D.R. KISS-1, a novel human malignant melanoma metastasis-suppressor gene. J. Natl. Cancer Inst. 1996, 88, 1731-1737.
12. Hori, A.; Honda, S.; Asada, M.; Ohtaki, T.; Oda, K.; Watanabe, T.; Shintani, Y.; Yamada, T.; Suenaga, M.; Kitada, C.; et al. Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem. Biophys. Res. Commun. 2001, 286, 958-963.
13. Hinuma, S.; Shintani, Y.; Fukusumi, S.; Iijima, N.; Matsumoto, Y.; Hosoya, M.; Fujii, R.; Watanabe, T.; Kikuchi, K.; Terao, Y.; et al. New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat. Cell. Biol. 2000, 2, 703-708.
14. Chartrel, N.; Dujardin, C.; Anouar, Y.; Leprince, J.; Decker, A.; Clerens, S.; Do-Rego, J.C.; Vandesande, F.; Llorens-Cortes, C.; Costentin, J.; et al. Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity. Proc. Natl. Acad. Sci. USA 2003, 100, 15247-15252.
15. Ohtaki, T.; Shintani, Y.; Honda, S.; Matsumoto, H.; Hori, A.; Kanehashi, K.; Terao, Y.; Kumano, S.; Takatsu, Y.; Masuda, Y.; et al. Metastasis suppressor gene KISS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 2001, 411, 613-617.
16. Bonini, J.A.; Jones, K.A.; Adham, N.; Forray, C.; Artymyshyn, R.; Durkin, M.M.; Smith, K.E.; Tamm, J.A.; Boteju, L.W.; Lakhlani, P.P.; et al. Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J. Biol. Chem. 2000, 275, 39324-39331.
17. Elshourbagy, N.A.; Ames, R.S.; Fitzgerald, L.R.; Foley, J.J.; Chambers, J.K.; Szekeres, P.G.; Evans, N.A.; Schmidt, D.B.; Buckley, P.T.; Dytko, G.M.; et al. Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor. J. Biol. Chem. 2000, 275, 25965-25971.
18. Fukusumi, S.; Yoshida, H.; Fujii, R.; Maruyama, M.; Komatsu, H.; Habata, Y.; Shintani, Y.; Hinuma, S.; Fujino, M. A new peptidic ligand and its receptor regulating adrenal function in rats. J. Biol. Chem. 2003, 278, 46387-46395.
19. Jiang, Y.; Luo, L.; Gustafson, E.L.; Yadav, D.; Laverty, M.; Murgolo, N.; Vassileva, G.; Zeng, M.; Laz, T.M.; Behan, J.; et al. Identification and characterization of a novel RF-amide peptide ligand for orphan G-protein-coupled receptor SP9155. J. Biol. Chem. 2003, 278, 27652-27657.
20. Muir, A.I.; Chamberlain, L.; Elshourbagy, N.A.; Michalovich, D.; Moore, D.J.; Calamari, A.; Szekeres, P.G.; Sarau, H.M.; Chambers, J.K.; Murdock, P.; et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KISS-1. J. Biol. Chem. 2001, 276, 28969-28975.
21. Parker, R.M.; Copeland, N.G.; Eyre, H.J.; Liu, M.; Gilbert, D.J.; Crawford, J.; Couzens, M.; Sutherland, G.R.; Jenkins, N.A.; Herzog, H. Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family. Brain Res. Mol. Brain Res. 2000, 77, 199-208.
22. Lee, D.K.; Nguyen, T.; O'Neill, G.P.; Cheng, R.; Liu, Y.; Howard, A.D.; Coulombe, N.; Tan, C.P.; Tang-Nguyen, A.T.; George, S.R.; et al. Discovery of a receptor related to the galanin receptors. FEBS Lett. 1999, 446, 103-107.
23. Ballesteros, J.A.; Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein coupled receptors. Methods Neurosci. 1995, 25, 366-428.
24. Goncharuk, V.; Zeng, Z.; Wang, R.; MacTavish, D.; Jhamandas, J.H. Distribution of the neuropeptide FF1 receptor (hFF1) in the human hypothalamus and surrounding basal forebrain structures: Immunohistochemical study. J. Comp. Neurol. 2004, 474, 487-503.
25. Kersante, F.; Mollereau, C.; Zajac, J.M.; Roumy, M. Anti-opioid activities of NPFF1 receptors in a SH-SY5Y model. Peptides 2006, 27, 980-989.
26. Gouarderes, C.; Mazarguil, H.; Mollereau, C.; Chartrel, N.; Leprince, J.; Vaudry, H.; Zajac, J.M. Functional differences between NPFF1 and NPFF2 receptor coupling: High intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPgammaS binding. Neuropharmacology 2007, 52, 376-386.
27. Merten, N.; Lindner, D.; Rabe, N.; Rompler, H.; Morl, K.; Schoneberg, T.; Beck-Sickinger, A.G. Receptor subtype-specific docking of Asp6.59 with C-terminal arginine residues in Y receptor ligands. J. Biol. Chem. 2007, 282, 7543-7551.
28. Findeisen, M.; Rathmann, D.; Beck-Sickinger, A.G. Structure-activity studies of RFamide peptides reveal subtype-selective activation of neuropeptide FF1 and FF2 receptors. ChemMedChem 2011, 6, 1081-1093.
29. Dupouy, V.; Zajac, J.M. Neuropeptide ff receptors in rat brain: A quantitative light-microscopic autoradiographic study using [125I][D. Tyr1, (NMe)Phe3]NPFF. Synapse 1996, 24, 282-296.
30. Gouarderes, C.; Tafani, J.A.; Mazarguil, H.; Zajac, J.M. Autoradiographic characterization of rat spinal neuropeptide FF receptors by using [125I][D. Tyr1, (NMe)Phe3]NPFF. Brain Res. Bull. 1997, 42, 231-238.
31. Mollereau, C.; Mazarguil, H.; Zajac, J.M.; Roumy, M. Neuropeptide FF (NPFF) analogs functionally antagonize opioid activities in NPFF receptor-transfected SH-SY5Y neuroblastoma cells. Mol. Pharmacol. 2005, 67, 965-975.
32. Mead, E.J.; Maguire, J.J.; Kuc, R.E.; Davenport, A.P. Kisspeptins are novel potent vasoconstrictors in humans, with a discrete localization of their receptor, G protein-coupled receptor 54, to atherosclerosis-prone vessels. Endocrinology 2007, 148, 140-147.
33. Chu, M.; Xiao, C.; Feng, T.; Fu, Y.; Cao, G.; Fang, L.; di, R.; Tang, Q.; Huang, D.; Ma, Y.; et al. Polymorphisms of KISS-1 and GPR54 genes and their relationships with litter size in sheep. Mol. Biol. Rep. 2011.
34. Nimri, R.; Lebenthal, Y.; Lazar, L.; Chevrier, L.; Phillip, M.; Bar, M.; Hernandez-Mora, E.; de Roux, N.; Gat-Yablonski, G. A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family. J. Clin. Endocrinol. Metab. 2011, 96, E536-E545.
35. Welch, S.K.; O'Hara, B.F.; Kilduff, T.S.; Heller, H.C. Sequence and tissue distribution of a candidate G-coupled receptor cloned from rat hypothalamus. Biochem. Biophys. Res. Commun. 1995, 209, 606-613.
36. Fujii, R.; Fukusumi, S.; Hosoya, M.; Kawamata, Y.; Habata, Y.; Hinuma, S.; Sekiguchi, M.; Kitada, C.; Kurokawa, T.; Nishimura, O.; et al. Tissue distribution of prolactin-releasing peptide (PrRP) and its receptor. Regul. Pept. 1999, 83, 1-10.
37. Lin, S.H.; Arai, A.C.; Wang, Z.; Nothacker, H.P.; Civelli, O. The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering. Mol. Pharmacol. 2001, 60, 916-923.
38. Gouarderes, C.; Sutak, M.; Zajac, J.M.; Jhamandas, K. Antinociceptive effects of intrathecally administered F8Famide and FMRFamide in the rat. Eur. J. Pharmacol. 1993, 237, 73-81.
39. Laguzzi, R.; Nosjean, A.; Mazarguil, H.; Allard, M. Cardiovascular effects induced by the stimulation of neuropeptide FF receptors in the dorsal vagal complex: An autoradiographic and pharmacological study in the rat. Brain Res. 1996, 711, 193-202.
40. Fang, Q.; Li, N.; Jiang, T.N.; Liu, Q.; Li, Y.L.; Wang, R. Pressor and tachycardic responses to intrathecal administration of neuropeptide FF in anesthetized rats. Peptides 2010, 31, 683-688.
41. Allard, M.; Labrouche, S.; Nosjean, A.; Laguzzi, R. Mechanisms underlying the cardiovascular responses to peripheral administration of NPFF in the rat. J. Pharmacol. Exp. Ther. 1995, 274, 577-583.
42. Huang, E.Y.; Li, J.Y.; Tan, P.P.; Wong, C.H.; Chen, J.C. The cardiovascular effects of PFRFamide and PFR(Tic)amide, a possible agonist and antagonist of neuropeptide FF (NPFF). Peptides 2000, 21, 205-210.
43. Jhamandas, J.H.; Harris, K.H.; Petrov, T.; Yang, H.Y.; Jhamandas, K.H. Activation of neuropeptide FF neurons in the brainstem nucleus tractus solitarius following cardiovascular challenge and opiate withdrawal. J. Comp. Neurol. 1998, 402, 210-221.
44. Roth, B.L.; Disimone, J.; Majane, E.A.; Yang, H.Y. Elevation of arterial pressure in rats by two new vertebrate peptides FLFQPQRF-NH2 and AGEGLSSPFWSLAAPQRF-NH2 which are immunoreactive to FMRF-NH2 antiserum. Neuropeptides 1987, 10, 37-42.
45. Jhamandas, J.H.; MacTavish, D. Central administration of neuropeptide FF causes activation of oxytocin paraventricular hypothalamic neurones that project to the brainstem. J. Neuroendocrinol. 2003, 15, 24-32.
46. Murase, T.; Arima, H.; Kondo, K.; Oiso, Y. Neuropeptide FF reduces food intake in rats. Peptides 1996, 17, 353-354.
47. Sunter, D.; Hewson, A.K.; Lynam, S.; Dickson, S.L. Intracerebroventricular injection of neuropeptide FF, an opioid modulating neuropeptide, acutely reduces food intake and stimulates water intake in the rat. Neurosci. Lett. 2001, 313, 145-148.
48. Cline, M.A.; Nandar, W.; Rogers, J.O. Central neuropeptide FF reduces feed consumption and affects hypothalamic chemistry in chicks. Neuropeptides 2007, 41, 433-439.
49. Cline, M.A.; Newmyer, B.A.; Smith, M.L. The anorectic effect of neuropeptide AF is associated with satiety-related hypothalamic nuclei. J. Neuroendocrinol. 2009, 21, 595-601.
50. Cline, M.A.; Godlove, D.C.; Nandar, W.; Bowden, C.N.; Prall, B.C. Anorexigenic effects of central neuropeptide S involve the hypothalamus in chicks (Gallus gallus). Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2007, 148, 657-663.
51. Bechtold, D.A.; Luckman, S.M. The role of RFamide peptides in feeding. J. Endocrinol. 2007, 192, 3-15.
52. Dockray, G.J. The expanding family of-RFamide peptides and their effects on feeding behaviour. Exp. Physiol. 2004, 89, 229-235.
53. Majane, E.A.; Yang, H.Y. Mammalian FMRF-NH2-like peptide in rat pituitary: Decrease by osmotic stimulus. Peptides 1991, 12, 1303-1308.
54. Sunter, D.; Hewson, A.K.; Lynam, S.; Dickson, S.L. Intracerebroventricular injection of neuropeptide FF, an opioid modulating neuropeptide, acutely reduces food intake and stimulates water intake in the rat. Neurosci. Lett. 2001, 313, 145-148.
55. Herrera-Herrera, M.L.; Salazar-Olivo, L.A. RFamide neuropeptides inhibit murine and human adipose differentiation. Biochem. Biophys. Res. Commun. 2008, 377, 29-34.
56. Kersante, F.; Wang, J.Y.; Chen, J.C.; Mollereau, C.; Zajac, J.M. Anti-opioid effects of neuropeptide FF receptors in the ventral tegmental area. Neurosci. Lett. 2011, 488, 305-309.
57. Wu, C.H.; Tao, P.L.; Huang, E.Y. Distribution of neuropeptide FF (NPFF) receptors in correlation with morphine-induced reward in the rat brain. Peptides 2010, 31, 1374-1382.
58. Mouledous, L.; Frances, B.; Zajac, J.M. Modulation of basal and morphine-induced neuronal activity by a NPFF(2) selective agonist measured by c-Fos mapping of the mouse brain. Synapse 2010, 64, 672-681.
59. Betourne, A.; Marty, V.; Ceccom, J.; Halley, H.; Lassalle, J.M.; Zajac, J.M.; Frances, B.; Mouledous, L. Central locomotor and cognitive effects of a NPFF receptor agonist in mouse. Peptides 2010, 31, 221-226.
60. Desprat, C.; Zajac, J.M. Hypothermic effects of neuropeptide FF analogues in mice. Pharmacol. Biochem. Behav. 1997, 58, 559-563.
61. Frances, B.; Lahlou, H.; Zajac; J.M. Cholera and pertussis toxins inhibit differently hypothermic and anti-opioid effects of neuropeptide FF. Regul. Pept. 2001, 98, 13-18.
62. Quelven, I.; Roussin, A.; Zajac, J.M. Comparison of pharmacological activities of neuropeptide FF1 and neuropeptide FF2 receptor agonists. Eur. J. Pharmacol. 2005, 508, 107-114.
63. Mouledous, L.; Barthas, F.; Zajac, J.M. Opposite control of body temperature by NPFF1 and NPFF2 receptors in mice. Neuropeptides 2010, 44, 453-456.
64. Fang, Q.; Guo, J.; He, F.; Peng, Y.L.; Chang, M.; Wang, R. In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist. Peptides 2006, 27, 2207-2213.
65. Raffa, R.B.; Kim, A.; Rice, K.C.; de Costa, B.R.; Codd, E.E.; Rothman, R.B. Low affinity of FMRFamide and four FaRPs (FMRFamide-related peptides), including the mammalian-derived FaRPs F-8-Famide (NPFF) and A-18-Famide, for opioid mu, delta, kappa 1, kappa 2a, or kappa 2b receptors. Peptides 1994, 15, 401-404.
66. Gouarderes, C.; Tafani, J.A.; Zajac, J.M. Affinity of neuropeptide FF analogs to opioid receptors in the rat spinal cord. Peptides 1998, 19, 727-730.
67. Malin, D.H.; Lake, J.R.; Hammond, M.V.; Fowler, D.E.; Rogillio, R.B.; Brown, S.L.; Sims, J.L.; Leecraft, B.M.; Yang, H.Y. FMRF-NH2-like mammalian octapeptide: Possible role in opiate dependence and abstinence. Peptides 1990, 11, 969-972.
68. Lake, J.R.; Hammond, M.V.; Shaddox, R.C.; Hunsicker, L.M.; Yang, H.Y.; Malin, D.H. IgG from neuropeptide FF antiserum reverses morphine tolerance in the rat. Neurosci. Lett. 1991, 132, 29-32.
69. Oberling, P.; Stinus, L.; Le Moal, M.; Simonnet, G. Biphasic effect on nociception and antiopiate activity of the neuropeptide FF (FLFQPQRFamide) in the rat. Peptides 1993, 14, 919-924.
70. Vergoni, A.V.; Watanobe, H.; Guidetti, G.; Savino, G.; Bertolini, A.; Schioth, H.B. Effect of repeated administration of prolactin releasing peptide on feeding behavior in rats. Brain Res. 2002, 955, 207-213.
71. Gu, W.; Geddes, B.J.; Zhang, C.; Foley, K.P.; Stricker-Krongrad, A. The prolactin-releasing peptide receptor (GPR10) regulates body weight homeostasis in mice. J. Mol. Neurosci. 2004, 22, 93-103.
72. Seal, L.J.; Small, C.J.; Dhillo, W.S.; Kennedy, A.R.; Ghatei, M.A.; Bloom, S.R. Prolactin-releasing peptide releases corticotropin-releasing hormone and increases plasma adrenocorticotropin via the paraventricular nucleus of the hypothalamus. Neuroendocrinology 2002, 76, 70-78.
73. Maruyama, M.; Matsumoto, H.; Fujiwara, K.; Noguchi, J.; Kitada, C.; Fujino, M.; Inoue, K. Prolactin-releasing peptide as a novel stress mediator in the central nervous system. Endocrinology 2001, 142, 2032-2038.
74. Lin, S.H.S.; Leslie, F.M.; Civelli, O. Neurochemical properties of the prolactin releasing peptide (PrRP) receptor expressing neurons: Evidence for a role of PrRP as a regulator of stress and nociception. Brain Res. 2002, 952, 15-30.
75. Samson, W.K.; Resch, Z.T.; Murphy, T.C. A novel action of the newly described prolactin-releasing peptides: Cardiovascular regulation. Brain Res. 2000, 858, 19-25.
76. Ma, L.; MacTavish, D.; Simonin, F.; Bourguignon, J.J.; Watanabe, T.; Jhamandas, J.H. Prolactin-releasing peptide effects in the rat brain are mediated through the neuropeptide FF receptor. Eur. J. Neurosci. 2009, 30, 1585-1593.
77. Matsumoto, H.; Maruyama, M.; Noguchi, J.; Horikoshi, Y.; Fujiwara, K.; Kitada, C.; Hinuma, S.; Onda, H.; Nishimura, O.; Inoue, K.; et al. Stimulation of corticotropin-releasing hormone-mediated adrenocorticotropin secretion by central administration of prolactin-releasing peptide in rats. Neurosci. Lett. 2000, 285, 234-238.
78. Yamada, T.; Mochiduki, A.; Sugimoto, Y.; Suzuki, Y.; Itoi, K.; Inoue, K. Prolactin-releasing peptide regulates the cardiovascular system via corticotrophin-releasing hormone. J. Neuroendocrinol. 2009, 21, 586-593.
79. Lawrence, C.B.; Liu, Y.L.; Stock, M.J.; Luckman, S.M. Anorectic actions of prolactin-releasing peptide are mediated by corticotropin-releasing hormone receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 286, R101-R107.
80. Harms, J.F.; Welch, D.R.; Miele, M.E. KISS1 metastasis suppression and emergent pathways. Clin. Exp. Metastasis 2003, 20, 11-18.
81. Gottsch, M.L.; Cunningham, M.J.; Smith, J.T.; Popa, S.M.; Acohido, B.V.; Crowley, W.F.; Seminara, S.; Clifton, D.K.; Steiner, R.A. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 2004, 145, 4073-4077.
82. Thompson, E.L.; Patterson, M.; Murphy, K.G.; Smith, K.L.; Dhillo, W.S.; Todd, J.F.; Ghatei, M.A.; Bloom, S.R. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J. Neuroendocrinol. 2004, 16, 850-858.
83. Messager, S.; Chatzidaki, E.E.; Ma, D.; Hendrick, A.G.; Zahn, D.; Dixon, J.; Thresher, R.R.; Malinge, I.; Lomet, D.; Carlton, M.B.; et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc. Natl. Acad. Sci. USA 2005, 102, 1761-1766.
84. Navarro, V.M.; Castellano, J.M.; Fernandez-Fernandez, R.; Tovar, S.; Roa, J.; Mayen, A.; Nogueiras, R.; Vazquez, M.J.; Barreiro, M.L.; Magni, P.; et al. Characterization of the potent luteinizing hormone-releasing activity of KISS-1 peptide, the natural ligand of GPR54. Endocrinology 2005, 146, 156-163.
85. de Roux, N.; Genin, E.; Carel, J.C.; Matsuda, F.; Chaussain, J.L.; Milgrom, E. Hypogonadotropic hypogonadism due to loss of function of the KISS1-derived peptide receptor GPR54. Proc. Natl. Acad. Sci. USA 2003, 100, 10972-10976.
86. Seminara, S.B.; Messager, S.; Chatzidaki, E.E.; Thresher, R.R.; Acierno, J.S., Jr.; Shagoury, J.K.; Bo-Abbas, Y.; Kuohung, W.; Schwinof, K.M.; Hendrick, A.G.; et al. The GPR54 gene as a regulator of puberty. N. Engl. J. Med. 2003, 349, 1614-1627.
87. Semple, R.K.; Achermann, J.C.; Ellery, J.; Farooqi, I.S.; Karet, F.E.; Stanhope, R.G.; O'Rahilly, S.; Aparicio, S.A. Two novel missense mutations in G protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2005, 90, 1849-1855.
88. Castellano, J.M.; Navarro, V.M.; Fernandez-Fernandez, R.; Nogueiras, R.; Tovar, S.; Roa, J.; Vazquez, M.J.; Vigo, E.; Casanueva, F.F.; Aguilar, E.; et al. Changes in hypothalamic KISS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology 2005, 146, 3917-3925.
89. Stengel, A.; Wang, L.; Goebel-Stengel, M.; Tache, Y. Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice. Neuroreport 2011, 22, 253-257.
90. Quennell, J.H.; Howell, C.S.; Roa, J.A.; Augustine, R.A.; Grattan, D.R.; Anderson, G.M. Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice. Endocrinology 2011, 152, 1541-1550.
91. Tena-Sempere, M.; Roa, J.; Aguilar, E.; Dieguez, C.; Pinilla, L. New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function. Front. Neuroendocrinol. 2008, 29, 48-69.
92. Popa, S.M.; Clifton, D.K.; Steiner, R.A. The role of kisspeptins and GPR54 in the neuroendocrine regulation of reproduction. Annu. Rev. Physiol. 2008, 70, 213-238.
93. Mead, E.J.; Maguire, J.J.; Kuc, R.E.; Davenport, A.P. Kisspeptins: A multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system. Br. J. Pharmacol. 2007, 151, 1143-1153.
94. Roseweir, A.K.; Millar, R.P. The role of kisspeptin in the control of gonadotrophin secretion. Hum. Reprod. Update 2009, 15, 203-212.
95. Kirby, H.R.; Maguire, J.J.; Colledge, W.H.; Davenport, A.P. International union of basic and clinical pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. Pharmacol. Rev. 2010, 62, 565-578.
96. Satake, H.; Hisada, M.; Kawada, T.; Minakata, H.; Ukena, K.; Tsutsui, K. Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release. Biochem. J. 2001, 354, 379-385.
97. Ducret, E.; Anderson, G.M.; Herbison, A.E. RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology 2009, 150, 2799-2804.
98. Murakami, M.; Matsuzaki, T.; Iwasa, T.; Yasui, T.; Irahara, M.; Osugi, T.; Tsutsui, K. Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats. J. Endocrinol. 2008, 199, 105-112.
99. Clarke, I.J.; Sari, I.P.; Qi, Y.; Smith, J.T.; Parkington, H.C.; Ubuka, T.; Iqbal, J.; Li, Q.; Tilbrook, A.; Morgan, K.; et al. Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion. Endocrinology 2008, 149, 5811-5821.
100. Johnson, M.A.; Tsutsui, K.; Fraley, G.S. Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat. Horm. Behav. 2007, 51, 171-180.
101. Qi, Y.; Oldfield, B.J.; Clarke, I.J. Projections of RFamide-related peptide-3 neurones in the ovine hypothalamus, with special reference to regions regulating energy balance and reproduction. J. Neuroendocrinol. 2009, 21, 690-697.
102. Liu, Q.; Guan, X.M.; Martin, W.J.; McDonald, T.P.; Clements, M.K.; Jiang, Q.; Zeng, Z.; Jacobson, M.; Williams, D.L., Jr.; Yu, H.; et al. Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception. J. Biol. Chem. 2001, 276, 36961-36969.
103. Roumy, M.; Garnier, M.; Zajac, J.M. Neuropeptide FF receptors 1 and 2 exert an anti-opioid activity in acutely dissociated rat dorsal raphe and periventricular hypothalamic neurones. Neurosci. Lett. 2003, 348, 159-162.
104. Cline, M.A.; Bowden, C.N.; Calchary, W.A.; Layne, J.E. Short-term anorexigenic effects of central neuropeptide VF are associated with hypothalamic changes in chicks. J. Neuroendocrinol. 2008, 20, 971-977.
105. Cline, M.A.; Sliwa, L.N. Neuropeptide VF-associated satiety involves mu and kappa but not delta subtypes of opioid receptors in chicks. Neurosci. Lett. 2009, 455, 195-198.
106. Fang, Q.; Liu, Q.; Li, N.; Jiang, T.N.; Li, Y.L.; Yan, X.; Wang, R. Cardiovascular effects of intravenous administered 26RFa, a novel RFamide peptide ligand for GPR103, in anaesthetised rats. Eur. J. Pharmacol. 2009, 621, 61-66.
107. Takayasu, S.; Sakurai, T.; Iwasaki, S.; Teranishi, H.; Yamanaka, A.; Williams, S.C.; Iguchi, H.; Kawasawa, Y.I.; Ikeda, Y.; Sakakibara, I.; et al. A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. Proc. Natl. Acad. Sci. USA 2006, 103, 7438-7443.
108. Moriya, R.; Sano, H.; Umeda, T.; Ito, M.; Takahashi, Y.; Matsuda, M.; Ishihara, A.; Kanatani, A.; Iwaasa, H. RFamide peptide QRFP43 causes obesity with hyperphagia and reduced thermogenesis in mice. Endocrinology 2006, 147, 2916-2922.
109. do Rego, J.C.; Leprince, J.; Chartrel, N.; Vaudry, H.; Costentin, J. Behavioral effects of 26RFamide and related peptides. Peptides 2006, 27, 2715-2721.
110. Primeaux, S.D.; Blackmon, C.; Barnes, M.J.; Braymer, H.D.; Bray, G.A. Central administration of the RFamide peptides, QRFP-26 and QRFP-43, increases high fat food intake in rats. Peptides 2008, 29, 1994-2000.
111. Navarro, V.M.; Fernandez-Fernandez, R.; Nogueiras, R.; Vigo, E.; Tovar, S.; Chartrel, N.; Le Marec, O.; Leprince, J.; Aguilar, E.; Pinilla, L.; et al. Novel role of 26RFa, a hypothalamic RFamide orexigenic peptide, as putative regulator of the gonadotropic axis. J. Physiol. 2006, 573, 237-249.
112. Patel, S.R.; Murphy, K.G.; Thompson, E.L.; Patterson, M.; Curtis, A.E.; Ghatei, M.A.; Bloom, S.R. Pyroglutamylated RFamide peptide 43 stimulates the hypothalamic-pituitary-gonadal axis via gonadotropin-releasing hormone in rats. Endocrinology 2008, 149, 4747-4754.
113. Yamamoto, T.; Miyazaki, R.; Yamada, T. Intracerebroventricular administration of 26RFa produces an analgesic effect in the rat formalin test. Peptides 2009, 30, 1683-1688.
114. Yamamoto, T.; Miyazaki, R.; Yamada, T.; Shinozaki, T. Anti-allodynic effects of intrathecally and intracerebroventricularly administered 26RFa, an intrinsic agonist for GPR103, in the rat partial sciatic nerve ligation model. Peptides 2011, 32, 1262-1269.
115. Baribault, H.; Danao, J.; Gupte, J.; Yang, L.; Sun, B.; Richards, W.; Tian, H. The G-protein-coupled receptor GPR103 regulates bone formation. Mol. Cell. Biol. 2006, 26, 709-717.
116. Zhang, Q.; Qiu, P.; Arreaza, M.G.; Simon, J.S.; Golovko, A.; Laverty, M.; Vassileva, G.; Gustafson, E.L.; Rojas-Triana, A.; Bober, L.A.; et al. P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse. Genomics 2007, 90, 629-635.
117. Flohr, S.; Kurz, M.; Kostenis, E.; Brkovich, A.; Fournier, A.; Klabunde, T. Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J. Med. Chem. 2002, 45, 1799-1805.
118. Gicquel, S.; Mazarguil, H.; Desprat, C.; Allard, M.; Devillers, J.P.; Simonnet, G.; Zajac, J.M. Structure-activity study of neuropeptide FF: Contribution of N-terminal regions to affinity and activity. J. Med. Chem. 1994, 37, 3477-3481.
119. Mazarguil, H.; Gouarderes, C.; Tafani, J.A.; Marcus, D.; Kotani, M.; Mollereau, C.; Roumy, M.; Zajac, J.M. Structure-activity relationships of neuropeptide FF: Role of C-terminal regions. Peptides 2001, 22, 1471-1478.
120. Mollereau, C.; Mazarguil, H.; Marcus, D.; Quelven, I.; Kotani, M.; Lannoy, V.; Dumont, Y.; Quirion, R.; Detheux, M.; Parmentier, M.; et al. Pharmacological characterization of human NPFF(1) and NPFF(2) receptors expressed in CHO cells by using NPY Y(1) receptor antagonists. Eur. J. Pharmacol. 2002, 451, 245-256.
121. Yoshida, H.; Habata, Y.; Hosoya, M.; Kawamata, Y.; Kitada, C.; Hinuma, S. Molecular properties of endogenous RFamide-related peptide-3 and its interaction with receptors. Biochim. Biophys. Acta 2003, 1593, 151-157.
122. Gouarderes, C.; Quelven, I.; Mollereau, C.; Mazarguil, H.; Rice, S.Q.; Zajac, J.M. Quantitative autoradiographic distribution of NPFF1 neuropeptide FF receptor in the rat brain and comparison with NPFF2 receptor by using [125I]YVP and [(125I]EYF as selective radioligands. Neuroscience 2002, 115, 349-361.
123. Gaubert, G.; Bertozzi, F.; Kelly, N.M.; Pawlas, J.; Scully, A.L.; Nash, N.R.; Gardell, L.R.; Lameh, J.; Olsson, R. Discovery of selective nonpeptidergic neuropeptide FF2 receptor agonists. J. Med. Chem. 2009, 52, 6511-6514.
124. Ukena, K.; Vaudry, H.; Leprince, J.; Tsutsui, K. Molecular evolution and functional characterization of the orexigenic peptide 26RFa and its receptor in vertebrates. Cell Tissue Res. 2011, 343, 475-481.
125. Boyle, R.G.; Downham, R.; Ganguly, T.; Humphries, J.; Smith, J.; Travers, S. Structure-activity studies on prolactin-releasing peptide (PrRP). Analogues of PrRP-(19-31)-peptide. J. Pept. Sci. 2005, 11, 161-165.
126. Le Marec, O.; Neveu, C.; Lefranc, B.; Dubessy, C.; Boutin, J.A.; Do-Rego, J.C.; Costentin, J.; Tonon, M.C.; Tena-Sempere, M.; Vaudry, H.; et al. Structure-activity relationships of a series of analogues of the RFamide-related peptide 26RFa. J. Med. Chem. 2011, 54, 4806-4814.
127. Thuau, R.; Guilhaudis, L.; Segalas-Milazzo, I.; Chartrel, N.; Oulyadi, H.; Boivin, S.; Fournier, A.; Leprince, J.; Davoust, D.; Vaudry, H. Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity. Peptides 2005, 26, 779-789.
128. Engstrom, M.; Brandt, A.; Wurster, S.; Savola, J.M.; Panula, P. Prolactin releasing peptide has high affinity and efficacy at neuropeptide FF2 receptors. J. Pharmacol. Exp. Ther. 2003, 305, 825-832.
129. Roland, B.L.; Sutton, S.W.; Wilson, S.J.; Luo, L.; Pyati, J.; Huvar, R.; Erlander, M.G.; Lovenberg, T.W. Anatomical distribution of prolactin-releasing peptide and its receptor suggests additional functions in the central nervous system and periphery. Endocrinology 1999, 140, 5736-5745.
130. Danho, W.; Swistok, J.; Khan, W.; Truitt, T.; Kurylko, G.; Fry, D.; Greeley, D.; Sun, H.; Dvorozniak, M.; Machie, G.; et al. Structure-activity relationships and bioactive conformations of prolactine releasing peptides. Ligands for a potential obesity target. In Proceedings of the 18th American Peptide Symposium, Boston, MA, USA, July 2003; pp. 750-751.
131. D'Ursi, A.M.; Albrizio, S.; di Fenza, A.; Crescenzi, O.; Carotenuto, A.; Picone, D.; Novellino, E.; Rovero, P. Structural studies on Hgr3 orphan receptor ligand prolactin-releasing peptide. J. Med. Chem. 2002, 45, 5483-5491.
132. Maletinska, L.; Spolcova, A.; Maixnerova, J.; Blechova, M.; Zelezna, B. Biological properties of prolactin-releasing peptide analogs with modified aromatic ring of C-terminal phenylalanine amide. Biopolymers 2011, 96, 481-481.
133. Gutierrez-Pascual, E.; Leprince, J.; Martinez-Fuentes, A.J.; Segalas-Milazzo, I.; Pineda, R.; Roa, J.; Duran-Prado, M.; Guilhaudis, L.; Desperrois, E.; Lebreton, A.; et al. In vivo and in vitro structure-activity relationships and structural conformation of kisspeptin-10-related peptides. Mol. Pharmacol. 2009, 76, 58-67.
134. Tomita, K.; Niida, A.; Oishi, S.; Ohno, H.; Cluzeau, J.; Navenot, J.M.; Wang, Z.X.; Peiper, S.C.; Fujii, N. Structure-activity relationship study on small peptidic GPR54 agonists. Bioorg. Med. Chem. 2006, 14, 7595-7603.
135. Niida, A.; Wang, Z.; Tomita, K.; Oishi, S.; Tamamura, H.; Otaka, A.; Navenot, J.M.; Broach, J.R.; Peiper, S.C.; Fujii, N. Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity. Bioorg. Med. Chem. Lett. 2006, 16, 134-137.
136. Orsini, M.J.; Klein, M.A.; Beavers, M.P.; Connolly, P.J.; Middleton, S.A.; Mayo, K.H. Metastin (KISS-1) mimetics identified from peptide structure-activity relationship-derived pharmacophores and directed small molecule database screening. J. Med. Chem. 2007, 50, 462-471.
137. Clements, M.K.; McDonald, T.P.; Wang, R.; Xie, G.; O'Dowd, B.F.; George, S.R.; Austin, C.P.; Liu, Q. FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54. Biochem. Biophys. Res. Commun. 2001, 284, 1189-1193.
138. Oishi, S.; Misu, R.; Tomita, K.; Setsuda, S.; Masuda, R.; Ohno, H.; Naniwa, Y.; Ieda, N.; Inoue, N.; Ohkura, S.; et al. Activation of neuropeptide FF receptors by kisspeptin receptor ligands. ACS Med. Chem. Lett. 2011, 2, 53-57.
139. Tomita, K.; Oishi, S.; Ohno, H.; Peiper, S.C.; Fujii, N. Development of novel G-protein-coupled receptor 54 agonists with resistance to degradation by matrix metalloproteinase. J. Med. Chem. 2008, 51, 7645-7649.
140. Tomita, K.; Oishi, S.; Cluzeau, J.; Ohno, H.; Navenot, J.M.; Wang, Z.X.; Peiper, S.C.; Akamatsu, M.; Fujii, N. SAR and QSAR studies on the N-terminally acylated pentapeptide agonists for GPR54. J. Med. Chem. 2007, 50, 3222-3228.
141. Tomita, K.; Narumi, T.; Niida, A.; Oishi, S.; Ohno, H.; Fujii, N. Fmoc-based solid-phase synthesis of GPR54-agonistic pentapeptide derivatives containing alkene-and fluoroalkene-dipeptide isosteres. Biopolymers 2007, 88, 272-278.
142. Curtis, A.E.; Cooke, J.H.; Baxter, J.E.; Parkinson, J.R.; Bataveljic, A.; Ghatei, M.A.; Bloom, S.R.; Murphy, K.G. A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10. Am. J. Physiol. Endocrinol. Metab. 2010, 298, E296-E303.
143. Ebling, F.J.; Luckman, S.M. RFamide-related peptide: Another sexy peptide? Endocrinology 2008, 149, 899-901.
144. Osugi, T.; Ukena, K.; Sower, S.A.; Kawauchi, H.; Tsutsui, K. Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides in the RFamide peptide family. Insights from novel lamprey RFamide peptides. FEBS J. 2006, 273, 1731-1743.
145. Lagerstrom, M.C.; Fredriksson, R.; Bjarnadottir, T.K.; Fridmanis, D.; Holmquist, T.; Andersson, J.; Yan, Y.L.; Raudsepp, T.; Zoorob, R.; Kukkonen, J.P.; et al. Origin of the prolactin-releasing hormone (PRLH) receptors: Evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution. Genomics 2005, 85, 688-703.
146. Malin, D.H.; Lake, J.R.; Leyva, J.E.; Hammond, M.V.; Rogillio, R.B.; Arcangeli, K.R.; Ludgate, K.; Moore, G.M.; Payza, K. Analog of neuropeptide FF attenuates morphine abstinence syndrome. Peptides 1991, 12, 1011-1014.
147. Malin, D.H.; Lake, J.R.; Smith, D.A.; Jones, J.A.; Morel, J.; Claunch, A.E.; Stevens, P.A.; Payza, K.; Ho, K.K.; Liu, J.; et al. Subcutaneous injection of an analog of neuropeptide FF prevents naloxone-precipitated morphine abstinence syndrome. Drug Alcohol. Depend. 1995, 40, 37-42.
148. Prokai, L.; Prokai-Tatrai, K.; Zharikova, A.; Li, X.; Rocca, J.R. Combinatorial lead optimization of a neuropeptide FF antagonist. J. Med. Chem. 2001, 44, 1623-1626.
149. Tan, P.P.; Chen, J.C.; Li, J.Y.; Liang, K.W.; Wong, C.H.; Huang, E.Y. Modulation of naloxone-precipitated morphine withdrawal syndromes in rats by neuropeptide FF analogs. Peptides 1999, 20, 1211-1217.
150. Doods, H.N.; Wieland, H.A.; Engel, W.; Eberlein, W.; Willim, K.D.; Entzeroth, M.; Wienen, W.; Rudolf, K. BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: A review of its pharmacological properties. Regul. Pept. 1996, 65, 71-77.
151. Engstrom, M.; Wurster, S.; Savola, J.M.; Panula, P. Functional properties of Pfr(Tic)amide and BIBP3226 at human neuropeptide FF2 receptors. Peptides 2003, 24, 1947-1954.
152. Fang, Q.; Guo, J.; Chang, M.; Chen, L.X.; Chen, Q.; Wang, R. Neuropeptide FF receptors exert contractile activity via inhibition of nitric oxide release in the mouse distal colon. Peptides 2005, 26, 791-797.
153. Mollereau, C.; Gouarderes, C.; Dumont, Y.; Kotani, M.; Detheux, M.; Doods, H.; Parmentier, M.; Quirion, R.; Zajac, J.M. Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226. Br. J. Pharmacol. 2001, 133, 1-4.
154. Iyengar, S.; Li, D.L.; Simmons, R.M., Characterization of neuropeptide Y-induced feeding in mice: Do Y1-Y6 receptor subtypes mediate feeding? J. Pharmacol. Exp. Ther. 1999, 289, 1031-1040.
155. Morgan, D.G.; Small, C.J.; Abusnana, S.; Turton, M.; Gunn, I.; Heath, M.; Rossi, M.; Goldstone, A.P.; O'Shea, D.; Meeran, K.; et al. The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism. Regul. Pept. 1998, 75-76, 377-382.
156. Bourguignon, J.; Schmitt, M.; Becker, P. Dipeptide ligands of the NPFFreceptor for treating pain and hyperalgesia. WO Patent: WO/2002/024192, 2002.
157. Simonin, F.; Schmitt, M.; Laulin, J.P.; Laboureyras, E.; Jhamandas, J.H.; MacTavish, D.; Matifas, A.; Mollereau, C.; Laurent, P.; Parmentier, M.; et al. RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia. Proc. Natl. Acad. Sci. USA 2006, 103, 466-471.
158. Fang, Q.; Wang, Y.Q.; He, F.; Guo, J.; Chen, Q.; Wang, R. Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist. Regul. Pept. 2008, 147, 45-51.
159. Jhamandas, J.H.; Simonin, F.; Bourguignon, J.J.; Harris, K.H. Neuropeptide FF and neuropeptide VF inhibit gabaergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292, R1872-R1880.
160. Roussin, A.; Serre, F.; Gouarderes, C.; Mazarguil, H.; Roumy, M.; Mollereau, C.; Zajac, J.M. Anti-analgesia of a selective NPFF2 agonist depends on opioid activity. Biochem. Biophys. Res. Commun. 2005, 336, 197-203.
161. Synaptic Pharmaceuticals Corp; Kawakami, J.; Wetzel, J.; Boteju, L.; Konkel, M.; Wan, H.; Noble, S., Guanidines which are agonist/antagonist ligands for neuropeptide FF (NPFF) receptors. WO Patent: WO2003026667A1, 2003.
162. Caroff, E.; Steger, M.; Valdenaire, O.; Fecher, A.; Breu, V.; Hilpert, K.; Fretz, H.; Giller, T. Guanidine derivatives and use thereof as neuropeptide FF receptor antagonists. EP Patent: EP20040722212, WO Patent: WO2004083218, 2004.
163. Fecher, A.; Fretz, H.; Hilpert, K.; Breu, V.; Giller, T.; Valdenaire, O. Guanidine derivatives. WO Patent: WO2005023781, 2005.
164. Actelion Pharmaceuticals, L.; Caroff, E.R.; Steger, M.S.G.; Valdenaire, O.A.; Fecher, A.A.; Breu, V.S.; Hilpert, K.H.; Fretz, H.R.; Giller, T.W. Guanidine derivatives and their use as neuropeptide FF receptor antagonists. US Patent: US 7,727,979 B2, 2010.
165. Roseweir, A.K.; Kauffman, A.S.; Smith, J.T.; Guerriero, K.A.; Morgan, K.; Pielecka-Fortuna, J.; Pineda, R.; Gottsch, M.L.; Tena-Sempere, M.; Moenter, S.M.; et al. Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation. J. Neurosci. 2009, 29, 3920-3929.
166. Pineda, R.; Garcia-Galiano, D.; Roseweir, A.; Romero, M.; Sanchez-Garrido, M.A.; Ruiz-Pino, F.; Morgan, K.; Pinilla, L.; Millar, R.P.; Tena-Sempere, M. Critical roles of kisspeptins in female puberty and preovulatory gonadotropin surges as revealed by a novel antagonist. Endocrinology 2010, 151, 722-730.
167. Kobayashi, T.; Sasaki, S.; Tomita, N.; Fukui, S.; Kuroda, N.; Nakayama, M.; Kiba, A.; Takatsu, Y.; Ohtaki, T.; Itoh, F.; et al. Synthesis and structure-activity relationships of 2-acylamino-4,6-diphenylpyridine derivatives as novel antagonists of GPR54. Bioorg. Med. Chem. 2010, 18, 3841-3859.
168. Kobayashi, T.; Sasaki, S.; Tomita, N.; Fukui, S.; Nakayama, M.; Kiba, A.; Kusaka, M.; Matsumoto, S.; Yamaguchi, M.; Itoh, F.; et al. 2-acylamino-4,6-diphenylpyridine derivatives as novel GPR54 antagonists with good brain exposure and in vivo efficacy for plasma LH level in male rats. Bioorg. Med. Chem. 2010, 18, 5157-5171.
169. Lameh, J.; Bertozzi, F.; Kelly, N.; Jacobi, P.M.; Nguyen, D.; Bajpai, A.; Gaubert, G.; Olsson, R.; Gardell, L.R. Neuropeptide FF receptors have opposing modulatory effects on nociception. J. Pharmacol. Exp. Ther. 2010, 334, 244-254.