Melanin-concentrating hormone receptor 1 explained

Melanin-concentrating hormone receptor 1, also known as MCH₁, is one of the melanin-concentrating hormone receptors found in all mammals.^[1]

The protein encoded by this gene, a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein which binds melanin-concentrating hormone. The encoded protein can inhibit cAMP accumulation and stimulate intracellular calcium flux, and is probably involved in the neuronal regulation of food consumption. Although structurally similar to somatostatin receptors, this protein does not seem to bind somatostatin.

Function

MCH₁ is thought to have a number of functions including in the regulation of appetite,^{[2] [3]} and in stress, anxiety and depression.^{[4] [5] [6] [7] [8] [9]}

Selective ligands

Agonists

• Melanin concentrating hormone (MCH)
• S-36057 - modified MCH 6-13 fragment substituted with 3-iodotyrosine at N-terminus via dioxyoctanoyl linker, used as ¹²⁵I radioligand for mapping MCH₁ in vivo.^{[10] [11]}
• LK-184 (Procter & Gamble) is one pick^[12]

Antagonists

• ATC-0065
• ATC-0175^[13]
• GW-803,430^[14]
• NGD-4715
• SNAP-7941^[15]
• SNAP-94847^[16]
• T-226,296^[17]

See also

• Melanin-concentrating hormone receptor

Further reading

• Kolakowski LF, Jung BP, Nguyen T, Johnson MP, Lynch KR, Cheng R, Heng HH, George SR, O'Dowd BF . Characterization of a human gene related to genes encoding somatostatin receptors . FEBS Letters . 398 . 2–3 . 253–8 . Dec 1996 . 8977118 . 10.1016/S0014-5793(96)01160-X . free .
• Chambers J, Ames RS, Bergsma D, Muir A, Fitzgerald LR, Hervieu G, Dytko GM, Foley JJ, Martin J, Liu WS, Park J, Ellis C, Ganguly S, Konchar S, Cluderay J, Leslie R, Wilson S, Sarau HM . Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1 . Nature . 400 . 6741 . 261–5 . Jul 1999 . 10421367 . 10.1038/22313 . 1999Natur.400..261C . 4361829 .
• Saito Y, Nothacker HP, Wang Z, Lin SH, Leslie F, Civelli O . Molecular characterization of the melanin-concentrating-hormone receptor . Nature . 400 . 6741 . 265–9 . Jul 1999 . 10421368 . 10.1038/22321 . 1999Natur.400..265S . 4408039 .
• Shimomura Y, Mori M, Sugo T, Ishibashi Y, Abe M, Kurokawa T, Onda H, Nishimura O, Sumino Y, Fujino M . Isolation and identification of melanin-concentrating hormone as the endogenous ligand of the SLC-1 receptor . Biochemical and Biophysical Research Communications . 261 . 3 . 622–6 . Aug 1999 . 10441476 . 10.1006/bbrc.1999.1104 .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . Dec 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
• Macdonald D, Murgolo N, Zhang R, Durkin JP, Yao X, Strader CD, Graziano MP . Molecular characterization of the melanin-concentrating hormone/receptor complex: identification of critical residues involved in binding and activation . Molecular Pharmacology . 58 . 1 . 217–25 . Jul 2000 . 10860944 . 10.1124/mol.58.1.217. 10757485 .
• An S, Cutler G, Zhao JJ, Huang SG, Tian H, Li W, Liang L, Rich M, Bakleh A, Du J, Chen JL, Dai K . Identification and characterization of a melanin-concentrating hormone receptor . Proceedings of the National Academy of Sciences of the United States of America . 98 . 13 . 7576–81 . Jun 2001 . 11416225 . 34710 . 10.1073/pnas.131200698 . 2001PNAS...98.7576A . free .
• Bednarek MA, Feighner SD, Hreniuk DL, Palyha OC, Morin NR, Sadowski SJ, MacNeil DJ, Howard AD, Van der Ploeg LH . Short segment of human melanin-concentrating hormone that is sufficient for full activation of human melanin-concentrating hormone receptors 1 and 2 . Biochemistry . 40 . 31 . 9379–86 . Aug 2001 . 11478907 . 10.1021/bi010867p .
• Bednarek MA, Tan C, Hreniuk DL, Palyha OC, MacNeil DJ, Van Der Ploeg LH, Howard AD, Feighner SD . Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1 . The Journal of Biological Chemistry . 277 . 16 . 13821–6 . Apr 2002 . 11839762 . 10.1074/jbc.M200563200 . free .
• Audinot V, Lahaye C, Suply T, Rovère-Jovène C, Rodriguez M, Nicolas JP, Beauverger P, Cardinaud B, Galizzi JP, Fauchère JL, Nahon JL, Boutin JA . SVK14 cells express an MCH binding site different from the MCH1 or MCH2 receptor . Biochemical and Biophysical Research Communications . 295 . 4 . 841–8 . Jul 2002 . 12127971 . 10.1016/S0006-291X(02)00763-5 .
• Hoogduijn MJ, Ancans J, Suzuki I, Estdale S, Thody AJ . Melanin-concentrating hormone and its receptor are expressed and functional in human skin . Biochemical and Biophysical Research Communications . 296 . 3 . 698–701 . Aug 2002 . 12176038 . 10.1016/S0006-291X(02)00932-4 .
• Bächner D, Kreienkamp HJ, Richter D . MIZIP, a highly conserved, vertebrate specific melanin-concentrating hormone receptor 1 interacting zinc-finger protein . FEBS Letters . 526 . 1–3 . 124–8 . Aug 2002 . 12208518 . 10.1016/S0014-5793(02)03115-0 . free .
• Verlaet M, Adamantidis A, Coumans B, Chanas G, Zorzi W, Heinen E, Grisar T, Lakaye B . Human immune cells express ppMCH mRNA and functional MCHR1 receptor . FEBS Letters . 527 . 1–3 . 205–10 . Sep 2002 . 12220661 . 10.1016/S0014-5793(02)03232-5 . 2268/26241 . free .
• Logan DW, Bryson-Richardson RJ, Pagán KE, Taylor MS, Currie PD, Jackson IJ . The structure and evolution of the melanocortin and MCH receptors in fish and mammals . Genomics . 81 . 2 . 184–91 . Feb 2003 . 12620396 . 10.1016/S0888-7543(02)00037-X .
• Pissios P, Trombly DJ, Tzameli I, Maratos-Flier E . Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways . Endocrinology . 144 . 8 . 3514–23 . Aug 2003 . 12865333 . 10.1210/en.2002-0004 . free .
• Gottumukkala RV, Waterman EA, Herd LM, Gawkrodger DJ, Watson PF, Weetman AP, Kemp EH . Autoantibodies in vitiligo patients recognize multiple domains of the melanin-concentrating hormone receptor . The Journal of Investigative Dermatology . 121 . 4 . 765–70 . Oct 2003 . 14632194 . 10.1046/j.1523-1747.2003.12494.x . free .
• Gibson WT, Pissios P, Trombly DJ, Luan J, Keogh J, Wareham NJ, Maratos-Flier E, O'Rahilly S, Farooqi IS . Melanin-concentrating hormone receptor mutations and human obesity: functional analysis . Obesity Research . 12 . 5 . 743–9 . May 2004 . 15166293 . 10.1038/oby.2004.89 . free .
• Hawes BE, Green B, O'Neill K, Fried S, Arreaza MG, Qiu P, Simon JS . Identification and characterization of single-nucleotide polymorphisms in MCH-R1 and MCH-R2 . Obesity Research . 12 . 8 . 1327–34 . Aug 2004 . 15340116 . 10.1038/oby.2004.167 .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .

External links

• Web site: Melanin-Concentrating Hormone Receptors: MCH₁ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology .

Notes and References

1. Web site: Entrez Gene: MCHR1 melanin-concentrating hormone receptor 1.
2. Luthin DR . Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists . Life Sciences . 81 . 6 . 423–40 . Jul 2007 . 17655875 . 10.1016/j.lfs.2007.05.029 .
3. Rivera G, Bocanegra-García V, Galiano S, Cirauqui N, Ceras J, Pérez S, Aldana I, Monge A . Melanin-concentrating hormone receptor 1 antagonists: a new perspective for the pharmacologic treatment of obesity . Current Medicinal Chemistry . 15 . 10 . 1025–43 . 2008 . 18393860 . 10.2174/092986708784049621 .
4. Hervieu G . Melanin-concentrating hormone functions in the nervous system: food intake and stress . Expert Opinion on Therapeutic Targets . 7 . 4 . 495–511 . Aug 2003 . 12885269 . 10.1517/14728222.7.4.495 . 25629841 .
5. Shimazaki T, Yoshimizu T, Chaki S . Melanin-concentrating hormone MCH1 receptor antagonists: a potential new approach to the treatment of depression and anxiety disorders . CNS Drugs . 20 . 10 . 801–11 . 2006 . 16999451 . 10.2165/00023210-200620100-00002 . 32524553 .
6. Hervieu GJ . Further insights into the neurobiology of melanin-concentrating hormone in energy and mood balances . Expert Opinion on Therapeutic Targets . 10 . 2 . 211–29 . Apr 2006 . 16548771 . 10.1517/14728222.10.2.211 . 37420990 .
7. Smith DG, Davis RJ, Rorick-Kehn L, Morin M, Witkin JM, McKinzie DL, Nomikos GG, Gehlert DR . Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice . Neuropsychopharmacology . 31 . 6 . 1135–45 . Jun 2006 . 16205780 . 10.1038/sj.npp.1300913 . free .
8. Roy M, David N, Cueva M, Giorgetti M . A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression . Biological Psychiatry . 61 . 2 . 174–80 . Jan 2007 . 16934771 . 10.1016/j.biopsych.2006.03.076 . 39334337 .
9. Book: Saito Y, Nagasaki H . The melanin-concentrating hormone system and its physiological functions . 46 . 159–79 . 2008 . 18227983 . 10.1007/400_2007_052 . 978-3-540-78350-3 . Results and Problems in Cell Differentiation . Orphan G Protein-Coupled Receptors and Novel Neuropeptides .
10. Audinot V, Lahaye C, Suply T, Beauverger P, Rodriguez M, Galizzi JP, Fauchère JL, Boutin JA . [125I]-S36057: a new and highly potent radioligand for the melanin-concentrating hormone receptor . British Journal of Pharmacology . 133 . 3 . 371–8 . Jun 2001 . 11375253 . 1572795 . 10.1038/sj.bjp.0704085 .
11. Able SL, Ivarsson M, Fish RL, Clarke TL, McCourt C, Duckworth JM, Napier C, Katugampola SD . Localisation of melanin-concentrating hormone receptor 1 in rat brain and evidence that sleep parameters are not altered despite high central receptor occupancy . European Journal of Pharmacology . 616 . 1–3 . 101–6 . Aug 2009 . 19540226 . 10.1016/j.ejphar.2009.06.009 .
12. 10.1016/j.bmcl.2004.05.039 . 14 . Analogs of sub-nanomolar hMC1R agonist LK-184 [Ph(CH2)3CO-His-d-Phe-Arg-Trp-NH2]. An additional binding site within the human melanocortin receptor 1? . 2004 . Bioorganic & Medicinal Chemistry Letters . 3997–4000 . Koikov LN, Ebetino FH, Solinsky MG, Cross-Doersen D, Knittel JJ. 15 . 15225714 .
13. Chaki S, Yamaguchi J, Yamada H, Thomsen W, Tran TA, Semple G, Sekiguchi Y . ATC0175: an orally active melanin-concentrating hormone receptor 1 antagonist for the potential treatment of depression and anxiety . CNS Drug Reviews . 11 . 4 . 341–52 . 2005 . 16614734 . 10.1111/j.1527-3458.2005.tb00052.x . 6741758 .
14. Gehlert DR, Rasmussen K, Shaw J, Li X, Ardayfio P, Craft L, Coskun T, Zhang HY, Chen Y, Witkin JM . Preclinical evaluation of melanin-concentrating hormone receptor 1 antagonism for the treatment of obesity and depression . The Journal of Pharmacology and Experimental Therapeutics . 329 . 2 . 429–38 . May 2009 . 19182070 . 10.1124/jpet.108.143362 . 7770969 .
15. Doggrell SA . Does the melanin-concentrating hormone antagonist SNAP-7941 deserve 3As? . Expert Opinion on Investigational Drugs . 12 . 6 . 1035–8 . Jun 2003 . 12783607 . 10.1517/13543784.12.6.1035 . 13219655 .
16. David DJ, Klemenhagen KC, Holick KA, Saxe MD, Mendez I, Santarelli L, Craig DA, Zhong H, Swanson CJ, Hegde LG, Ping XI, Dong D, Marzabadi MR, Gerald CP, Hen R . Efficacy of the MCHR1 antagonist N-[3-(1-<nowiki/>{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis . The Journal of Pharmacology and Experimental Therapeutics . 321 . 1 . 237–48 . Apr 2007 . 17237257 . 10.1124/jpet.106.109678 . 717425 .
17. Takekawa S, Asami A, Ishihara Y, Terauchi J, Kato K, Shimomura Y, Mori M, Murakoshi H, Kato K, Suzuki N, Nishimura O, Fujino M . T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist . European Journal of Pharmacology . 438 . 3 . 129–35 . Mar 2002 . 11909603 . 10.1016/S0014-2999(02)01314-6 .