Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Melatonin Receptor MT1 and MT2

  • Atsuro Oishi
  • Ralf JockersEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101751


Historical Background

Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionary old molecule which is derived from the essential amino acid tryptophan in a four-step biosynthesis pathway. Melatonin is synthesized by many organisms as diverse as bacteria, protists, fungi, macroalgae, plants, and animals. During evolution, several functions of melatonin appeared including protection of cells against oxidative stress, regulation of circadian rhythmicity, and ciliary swimming in invertebrates. The function of melatonin further expanded in mammals (see below). In mammals, the synthesis of melatonin is regulated by light and by...

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



We would like to acknowledge Dr. Erika Cecon for reading the manuscript and helpful suggestions.

This work was supported by the Fondation de la Recherche Médicale (Equipe FRM DEQ20130326503), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS) and the “Who am I?” laboratory of excellence No.ANR-11-LABX-0071 funded by the French Government through its “Investments for the Future” program operated by the French National Research Agency (ANR) under grant No.ANR-11-IDEX-0005-01.


  1. Ayoub MA, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M, et al. Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer. J Biol Chem. 2002;277:21522–8. doi:10.1074/jbc.M200729200.CrossRefPubMedGoogle Scholar
  2. Baba K, Benleulmi-Chaachoua A, Journe AS, Kamal M, Guillaume JL, Dussaud S, et al. Heteromeric MT1/MT2 melatonin receptors modulate photoreceptor function. Sci Signal. 2013;6:ra89. doi:10.1126/scisignal.2004302.CrossRefPubMedGoogle Scholar
  3. Bonnefond A, Clement N, Fawcett K, Yengo L, Vaillant E, Guillaume JL, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44:297–301. doi:10.1038/ng.1053.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 2010;62:343–80.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ebisawa T, Karne S, Lerner MR, Reppert SM. Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores. Proc Natl Acad Sci U S A. 1994;91:6133–7.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Jin X, von Gall C, Pieschl RL, Gribkoff VK, Stehle JH, Reppert SM, et al. Targeted disruption of the mouse Mel(1b) melatonin receptor. Mol Cell Biol. 2003;23:1054–60.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, et al. Update on melatonin receptors. IUPHAR Review. Br J Pharmacol. 2016. doi:10.1111/bph.13536.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kamal M, Gbahou F, Guillaume JL, Daulat AM, Benleulmi-Chaachoua A, Luka M, et al. Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor heteromers. J Biol Chem. 2015;290:11537–46. doi:10.1074/jbc.M114.559542.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Lerner AB, Case JD, Biemann K, Heinzelman R, Szmuszkovicz J, Anthony W, et al. Isolation of 5-methoxyindole-3-acetic acid from bovine pineal glands. J Am Chem Soc. 1959a;81:5264. doi:10.1021/ja01528a064.CrossRefGoogle Scholar
  10. Lerner AB, Case JD, Heinzelman RV. Structure of melatonin. J Am Chem Soc. 1959b;81:6084–5. doi:10.1021/ja01531a060.CrossRefGoogle Scholar
  11. Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, et al. The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO J. 2006;25:3012–23. doi:10.1038/sj.emboj.7601193.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, et al. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997;19:91–102.CrossRefPubMedGoogle Scholar
  13. Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annu Rev Pharmacol Toxicol. 2016;56:361–83. doi:10.1146/annurev-pharmtox-010814-124742.CrossRefPubMedGoogle Scholar
  14. Reppert SM, Weaver DR, Ebisawa T. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron. 1994;13:1177–85. doi: http://dx.doi.org/10.1016/0896-6273(94)90055-8.CrossRefPubMedGoogle Scholar
  15. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel(1b) melatonin receptor. Proc Natl Acad Sci U S A. 1995;92:8734–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Tosini G, Owino S, Guillaume JL, Jockers R. Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease. BioEssays : News Rev Mol Cell Dev Biol. 2014;36:778–87. doi:10.1002/bies.201400017.CrossRefGoogle Scholar
  17. Zlotos DP, Jockers R, Cecon E, Rivara S, Witt-Enderby PA. MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014;57:3161–85. doi:10.1021/jm401343c.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institut Cochin, INSERM, U1016, CNRS 8104, Université Paris DescartesParisFrance