Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Melanin-Concentrating Hormone Receptor 1 (MCHR1)

  • Akie Hamamoto
  • Yuki Kobayashi
  • Yumiko Saito
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101710

Synonyms

Historical Background

MCHR1 is a receptor for melanin-concentrating hormone (MCH). MCH was originally discovered from salmon pituitary as a 17-amino acid cyclic peptide (Kawauchi et al. 1983); in teleost fish, MCH causes the aggregation of melanosomes in the scales, which lightens skin color. The mammalian form of MCH is highly homologous to that of the teleost, but its expression is detected at high levels in the lateral hypothalamus, which is classically a feeding center (Bittencourt et al. 1992). Based on physiological and genetic experiments, MCH is strongly implicated in the regulation of feeding behavior and energy metabolism (Shimada et al. 1998).

Initial efforts to identify the receptor for MCH were based on binding assays by using radiolabeled MCH. MCH binding was detected in mouse melanoma...

This is a preview of subscription content, log in to check access.

References

  1. 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. Eur J Pharmacol. 2009;616:101–6.CrossRefPubMedGoogle Scholar
  2. Alon T, Friedman JM. Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. J Neurosci. 2006;26:389–97.CrossRefPubMedGoogle Scholar
  3. Antal-Zimanyi I, Khawaja X. The role of melanin-concentrating hormone in energy homeostasis and mood disorders. J Mol Neurosci. 2009;39:86–98.CrossRefPubMedGoogle Scholar
  4. Berbari NF, Johnson AD, Lewis JS, Askwith CC, Mykytyn K. Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell. 2008;19:1540–7.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, Vale W, Sawchenko PE. The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol. 1992;319:218–45.CrossRefPubMedGoogle Scholar
  6. 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. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med. 2002;8:825–30.CrossRefPubMedGoogle Scholar
  7. Chambers J, Ames RS, Bergsma D, Muir A, Fitzgerald LR, Hervieu G, Dytko GM, Foley JJ, Martin J, Liu WS, Park J, Ellis JC, 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. 1999;400:261–5.CrossRefPubMedGoogle Scholar
  8. Chen Y, Hu C, Hsu CK, Zhang Q, Bi C, Asnicar M, Hsiung HM, Fox N, Slieker LJ, Yang DD, Heiman ML, Shi Y. Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology. 2002;143:2469–77.CrossRefPubMedGoogle Scholar
  9. Civelli O. Orphan GPCRs and neuromodulation. Neuron. 2012;76:12–21.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Fan J, Perry SJ, Gao Y, Schwarz DA, Maki RA. A point mutation in the human melanin concentrating hormone receptor 1 reveals an important domain for cellular trafficking. Mol Endocrinol. 2005;19:2579–90.CrossRefPubMedGoogle Scholar
  11. Fredriksson R, Schiöth HB. The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol Pharmacol. 2005;67:1414–25.CrossRefPubMedGoogle Scholar
  12. Hamamoto A, Horikawa M, Saho T, Saito Y. Mutation of Phe318 within the NPxxY(x)(5,6)F motif in melanin-concentrating hormone receptor 1 results in an efficient signaling activity. Front Endocrinol (Lausanne). 2012;26:147.Google Scholar
  13. Hamamoto A, Kobayashi Y, Saito Y. Identification of amino acids that are selectively involved in Gi/o activation by rat melanin-concentrating hormone receptor 1. Cell Signal. 2015;27:818–27.CrossRefPubMedGoogle Scholar
  14. Hamamoto A, Yamato S, Katoh Y, Nakayama K, Yoshimura K, Takeda S, Kobayashi Y, Saito Y. Modulation of primary cilia length by melanin-concentrating hormone receptor 1. Cell Signal. 2016;28:572–84.CrossRefPubMedGoogle Scholar
  15. Hawes BE, Kil E, Green B, O’Neill K, Fried S, Graziano MP. The melanin-concentrating hormone couples to multiple G proteins to activate diverse intracellular signaling pathways. Endocrinology. 2000;141:4524–32.CrossRefPubMedGoogle Scholar
  16. Hervieu GJ, Cluderay JE, Harrison D, Meakin J, Maycox P, Nasir S, Leslie RA. The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. Eur J Neurosci. 2000;12:1194–216.CrossRefPubMedGoogle Scholar
  17. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. New Engl J Med. 2011;364:1533–43.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Kawauchi H, Kawazoe I, Tsubokaw M, Kishida M, Baker BL. Characterization of melanin-concentrating hormone in chum salmon pituitaries. Nature. 1983;305:321–3.CrossRefPubMedGoogle Scholar
  19. Kobayashi Y, Hamamoto A, Hirayama T, Saito Y. Molecular cloning, expression, and signaling pathway of four melanin-concentrating hormone receptors from Xenopus tropicalis. Gen Comp Endocrinol. 2015;212:114–23.CrossRefPubMedGoogle Scholar
  20. Luthin DR. Anti-obesity effects of small molecule melanin-concentrating hormone receptor 1 (MCHR1) antagonists. Life Sci. 2007;81:423–40.CrossRefPubMedGoogle Scholar
  21. 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. Mol Pharmacol. 2000;58:217–25.CrossRefPubMedGoogle Scholar
  22. Macneil DJ. The role of melanin-concentrating hormone and its receptors in energy homeostasis. Front Endocrinol (Lausanne). 2013;4:49.Google Scholar
  23. Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, Guan XM, Jiang MM, Feng Y, Camacho RE, Shen Z, Frazier EZ, Yu H, Metzger JM, Kuca SJ, Shearman LP, Gopal-Truter S, MacNeil DJ, Strack AM, MacIntyre DE, Van der Ploeg LH, Qian S. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A. 2002;99:3240–5.CrossRefGoogle Scholar
  24. Miyamoto-Matsubara M, Saitoh O, Maruyama K, Aizaki Y, Saito Y. Regulation of melanin-concentrating hormone receptor 1 signaling by RGS8 with the receptor third intracellular loop. Cell Signal. 2008;20:2084–94.CrossRefPubMedGoogle Scholar
  25. Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, Abe M, Shintani Y, Onda H, Nishimura O, Fujino M. Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun. 2001;283:1013–8.CrossRefPubMedGoogle Scholar
  26. Murdoch H, Feng GJ, Bachner D, Ormiston L, White JH, Richter D, Milligan G. Periplakin interferes with G protein activation by the melanin-concentrating hormone receptor-1 by binding to the proximal segment of the receptor C-terminal tail. J Biol Chem. 2005;280:8208–20.CrossRefPubMedGoogle Scholar
  27. Richter C, Woods IG, Schier AF. Neuropeptidergic control of sleep and wakefulness. Annu Rev Neurosci. 2014;37:503–31.CrossRefPubMedGoogle Scholar
  28. Saito Y, Nothacker HP, Wang Z, Lin S, Leslie FM, Civelli O. Molecular characterization of the melanin-concentrating-hormone receptor. Nature. 1999;400:265–9.CrossRefPubMedGoogle Scholar
  29. Saito Y, Cheng M, Leslie FM, Civelli O. Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol. 2001;435:26–40.CrossRefPubMedGoogle Scholar
  30. Saito Y, Tetsuka M, Saito S, Imai K, Yoshikawa A, Doi H, Maruyama K. Arginine residue 155 in the second intracellular loop plays a critical role in rat melanin-concentrating hormone receptor 1. Endocrinology. 2005;146:3452–62.CrossRefPubMedGoogle Scholar
  31. Schou KB, Pedersen LB, Christensen ST. Ins and outs of GPCR signaling in primary cilia. EMBO Rep. 2015;16:1099–113.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998;396:670–4.CrossRefPubMedGoogle Scholar
  33. 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. Eur J Pharmacol. 2002;438:129–35.CrossRefPubMedGoogle Scholar
  34. 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. Melanin-concentrating hormone receptor subtypes 1 and 2: species-specific gene expression. Genomics. 2002;79:785–92.CrossRefPubMedGoogle Scholar
  35. Tetsuka M, Saito Y, Imai K, Doi H, Maruyama K. The basic residues in the membrane-proximal C-terminal tail of the rat melanin-concentrating hormone receptor 1 are required for receptor function. Endocrinology. 2004;145:3712–23.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory for Behavioral Neuroscience, Graduate School of Integrated Arts and SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Molecular Genetics, Institute of Life ScienceKurume UniversityFukuokaJapan