Overview: Melanin-concentrating hormone (MCH) receptors (provisional nomenclature, see Foord et al., 2005) are activated by an endogenous nonadecameric cyclic peptide identical in humans and rats (DFDMLRCMLGRVYRPCWQV) generated from a precursor (ENSG00000183395), which also produces neuropeptides EI and GE.
| Nomenclature | MCH1 | MCH2 |
|---|---|---|
| Other names | SLC-1, GPR24 | SLT, GPRv17 |
| Ensembl ID | ENSG00000128285 | ENSG00000152034 |
| Principal transduction | Gq/11, Gi/o | Gq/11 (Hill et al., 2001); Mori et al., 2001; Rodriguez et al., 2001) |
| Rank order of potency | Human MCH > salmon MCH | Human MCH = salmon MCH (Hill et al., 2001) |
| Selective antagonists | SNAP7941 (9.2, Borowsky et al., 2002), ATC0175 (pIC50 7.9-8.2, Chaki et al., 2005), T226296 (7.5, Takekawa et al., 2002) | – |
| Probes | [3H]-MCH (Burgaud et al., 1997), [Phe13,[125I]-Tyr19]MCH (Burgaud et al., 1997), [125I]-S36057 (0.04 nM, Audinot et al., 2001) | – |
The MCH2 receptor appears to be a non-functional pseudogene in rodents (Tan et al., 2002).
Glossary
Abbreviations:
- ATC0175
N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino}cyclohexyl)-3,4-difluorobenzamide hydrochloride
- S36057
3-iodo-tyr-(8-amino-3,6-dioxyoctanoyl)MCH-(6-17)
- SNAP7941
(+)-methyl(4S)-3-([{3-(4-[3-{acetylamino}phenyl]-1-piperidinyl)propyl}amino]carbonyl)-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate hydrochloride
- T226296
(-)-N-[6-(dimethylamino)-methyl]-5,6,7,8-tetrahydro-2-naphthalenyl]-4′-fluoro[ 1,1′-biphenyl]-4-carboxamide
Further Reading
Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP et al. (2005). International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev57: 279–288.
Handlon AL, Zhou H (2006). Melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity. J Med Chem49: 4017–4022.
Kemp EH, Weetman AP (2009). Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology. Peptides30: 2071–2076.
Luthin DR (2007). Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life Sci81: 423–440.
Pissios P, Bradley RL, Maratos-Flier E (2006). Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions. Endocr Rev27: 606–620.
Rokosz LL, Hobbs DW (2006). Biological examination of melanin concentrating hormone receptor 1: multi-tasking from the hypothalamus. Drug News Perspect19: 273–286.
Saito Y, Nagasaki H (2008). The melanin-concentrating hormone system and its physiological functions. Results Probl Cell Differ46: 159–179.
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 Drugs20: 801–811.
References
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