Melanin-concentrating hormone (MCH) receptors (provisional nomenclature as recommended by NC-IUPHAR [5]) are activated by an endogenous nonadecameric cyclic peptide identical in humans and rats (DFDMLRCMLGRVYRPCWQV) generated from a precursor (PMCH, P20382), which also produces neuropeptide EI (PMCH, P20382) and neuropeptide GE (PMCH, P20382).

The MCH₂ receptor appears to be a non-functional pseudogene in rodents [11].

* Key recommended reading is highlighted with an asterisk

Antal-Zimanyi I, Khawaja X. (2009) The role of melanin-concentrating hormone in energy homeostasis and mood disorders. J. Mol. Neurosci., 39 (1-2): 86-98. [PMID:19418262]

Boughton CK, Murphy KG. (2013) Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity. Br. J. Pharmacol., 170 (7): 1333-48. [PMID:23121386]

* Chung S, Parks GS, Lee C, Civelli O. (2011) Recent updates on the melanin-concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists. J. Mol. Neurosci., 43 (1): 115-21. [PMID:20582487]

Chung S, Saito Y, Civelli O. (2009) MCH receptors/gene structure-in vivo expression. Peptides, 30 (11): 1985-9. [PMID:19647772]

* Eberle AN, Mild G, Zumsteg U. (2010) Cellular models for the study of the pharmacology and signaling of melanin-concentrating hormone receptors. J. Recept. Signal Transduct. Res., 30 (6): 385-402. [PMID:21083507]

* Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]

Gao XB. (2009) Electrophysiological effects of MCH on neurons in the hypothalamus. Peptides, 30 (11): 2025-30. [PMID:19463877]

Kemp EH, Weetman AP. (2009) Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology. Peptides, 30 (11): 2071-5. [PMID:19442695]

Lakaye B, Coumans B, Harray S, Grisar T. (2009) Melanin-concentrating hormone and immune function. Peptides, 30 (11): 2076-80. [PMID:19450627]

Luthin DR. (2007) Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life Sci., 81 (6): 423-40. [PMID:17655875]

Macneil DJ. (2013) The role of melanin-concentrating hormone and its receptors in energy homeostasis. Front Endocrinol (Lausanne), 4: 49. [PMID:23626585]

Parker JA, Bloom SR. (2012) Hypothalamic neuropeptides and the regulation of appetite. Neuropharmacology, 63 (1): 18-30. [PMID:22369786]

Pissios P. (2009) Animals models of MCH function and what they can tell us about its role in energy balance. Peptides, 30 (11): 2040-4. [PMID:19447150]

Pissios P, Bradley RL, Maratos-Flier E. (2006) The multiple roles of MCH in regulating energy balance and other biological functions. Endocr. Rev., 27: 606-620. [PMID:16788162]

Rokosz LL, Hobbs DW. (2006) Biological examination of melanin concentrating hormone receptor 1: multi-tasking from the hypothalamus. Drug News Perspect., 19 (5): 273-86. [PMID:16941049]

Saito Y, Nagasaki H. (2008) The melanin-concentrating hormone system and its physiological functions. Results Probl. Cell Differ., 46: 159-179. [PMID:18227983]

Shimazaki T, Yoshimizu T, Chaki S. (2006) Melanin-concentrating hormone MCH1 receptor antagonists: a potential new approach to the treatment of depression and anxiety disorders. CNS Drugs, 20 (10): 801-11. [PMID:16999451]

* Takase K, Kikuchi K, Tsuneoka Y, Oda S, Kuroda M, Funato H. (2014) Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes. PLoS ONE, 9 (6): e99961. [PMID:24924345]

1. Audinot V, Lahaye C, Suply T, Beauverger P, Rodriguez M, Galizzi JP, Fauchere JL, Boutin JA. (2001) [125I]-S36057: a new and highly potent radioligand for the melanin-concentrating hormone receptor. Br J Pharmacol, 133: 371-378. [PMID:11375253]

2. Borowsky B, Durkin MM, Ogozalek K, Marzabadi MR, DeLeon J, Lagu B, Heurich R, Lichtblau H, Shaposhnik Z, Daniewska I, Blackburn TP, Branchek TA, Gerald C, Vaysse PJ, Forray C. (2002) Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med, 8: 825-830. [PMID:12118247]

3. Burgaud JL, Poosti R, Fehrentz JA, Martinez J, Nahon JL. (1997) Melanin-concentrating hormone binding sites in human SVK14 keratinocytes. Biochem. Biophys. Res. Commun., 241 (3): 622-9. [PMID:9434758]

4. Chaki S, Funakoshi T, Hirota-Okuno S, Nishiguchi M, Shimazaki T, Iijima M, Grottick AJ, Kanuma K, Omodera K, Sekiguchi Y, Okuyama S, Tran TA, Semple G, Thomsen W. (2005) Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. J Pharmacol Exp Ther, 313: 831-839. [PMID:15677346]

5. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]

6. Hertzog DL, Al-Barazanji KA, Bigham EC, Bishop MJ, Britt CS, Carlton DL, Cooper JP, Daniels AJ, Garrido DM, Goetz AS et al.. (2006) The discovery and optimization of pyrimidinone-containing MCH R1 antagonists. Bioorg. Med. Chem. Lett., 16 (18): 4723-7. [PMID:16870432]

7. Hill J, Duckworth M, Murdock P, Rennie G, Sabido-David C, Ames RS, Szekeres P, Wilson S, Bergsma DJ, Gloger IS, Levy DS, Chambers JK, Muir AI. (2001) Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. J Biol Chem, 276: 20125-20129. [PMID:11274220]

8. Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, Abe M, Shintani Y, Onda H, Nishimura O, Fujino M. (2001) Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun, 283: 1013-1018. [PMID:11355873]

9. Rodriguez M, Beauverger P, Naime I, Rique H, Ouvry C, Souchaud S, Dromaint S, Nagel N, Suply T, Audinot V, Boutin JA, Galizzi JP. (2001) Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2. Mol Pharmacol, 60: 632-639. [PMID:11562423]

10. Takekawa S, Asami A, Ishihara Y, Terauchi J, Kato K, Shimomura Y, Mori M, Murakoshi H, Kato K, Suzuki N, Nishimura O, Fujino M. (2002) T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist. Eur J Pharmacol, 438: 129-135. [PMID:11909603]

11. Tan CP, Sano H, Iwaasa H, Pan J, Sailer AW, Hreniuk DL, Feighner SD, Palyha OC, Pong SS, Figueroa DJ, Austin CP, Jiang MM, Yu H, Ito J, Ito M, Ito M, Guan XM, MacNeil DJ, Kanatani A, Van der Ploeg LH, Howard AD. (2002) Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression. Genomics, 79: 785-792. [PMID:12036292]

Subcommittee members: Jean-Louis Nahon (Chairperson) Research Director/DR1 CNRS Director UPS 846 CNRS-SdP, Rousset GENE Team Leader IPMC UMR 7275 CNRS/UNS 660 route des lucioles, Sophia Antipolis 06560 Valbonne France Bernard Lakaye Research Associate FRS-FNRS Lab. of Experimental Neuropathy and Neurobiology GIGA-Neurosciences University of Liège 1, avenue de l’Hopital 4000 Liège Belgium Yumito Saito Graduate Sch Int Arts and Sciences Professor Hiroshima University 1-7-1 Kagamiyama Higashi-Hiroshima 7398521 Japan

Other contributors: Valérie Audinot Alliance Management Director, R & D Institut de recherches SERVIER 11, rue des Moulineaux Suresnes 92150 France Jean A. Boutin (Past chairperson) Pharmacologie Moléculaire et Cellulaire Institut de Recherches SERVIER 125 chemin de Ronde Croissy-sur-Seine 78290 France