More information on this family may be found on the IUPHAR-DB family and introduction pages.
Melatonin receptors (nomenclature as agreed by NC-IUPHAR Subcommittee on melatonin receptors, [6]) are activated by the endogenous ligands melatonin and N-acetylserotonin.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Alarma-Estrany, P; Pintor, J. (2007) Melatonin receptors in the eye: location, second messengers and role in ocular physiology. Pharmacol. Ther., 113 (3): 507-22. [PMID:17229466]
Ambriz-Tututi, M; Rocha-González, HI; Cruz, SL; Granados-Soto, V. (2009) Melatonin: a hormone that modulates pain. Life Sci., 84 (15-16): 489-98. [PMID:19223003]
de Bodinat, C; Guardiola-Lemaitre, B; Mocaër, E; Renard, P; Muñoz, C; Millan, MJ. (2010) Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. Nat Rev Drug Discov, 9 (8): 628-42. [PMID:20577266]
Dubocovich, ML; Delagrange, P; Krause, DN; Sugden, D; Cardinali, DP; Olcese, J. (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev., 62 (3): 343-80. [PMID:20605968]
Dufourny, L; Levasseur, A; Migaud, M; Callebaut, I; Pontarotti, P; Malpaux, B; Monget, P. (2008) GPR50 is the mammalian ortholog of Mel1c: evidence of rapid evolution in mammals. BMC Evol. Biol., 8: 105. [PMID:18400093]
Falcón, J; Besseau, L; Sauzet, S; Boeuf, G. (2007) Melatonin effects on the hypothalamo-pituitary axis in fish. Trends Endocrinol. Metab., 18 (2): 81-8. [PMID:17267239]
Hardeland, R. (2008) Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions and bioactive metabolites. Cell. Mol. Life Sci., 65 (13): 2001-18. [PMID:18344019]
Jockers, R; Maurice, P; Boutin, JA; Delagrange, P. (2008) Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?. Br. J. Pharmacol., 154 (6): 1182-95. [PMID:18493248]
Luchetti, F; Canonico, B; Betti, M; Arcangeletti, M; Pilolli, F; Piroddi, M; Canesi, L; Papa, S; Galli, F. (2010) Melatonin signaling and cell protection function. FASEB J., 24 (10): 3603-24. [PMID:20534884]
Reiter, RJ; Tan, DX; Fuentes-Broto, L. (2010) Melatonin: a multitasking molecule. Prog. Brain Res., 181: 127-51. [PMID:20478436]
Slominski, A; Tobin, DJ; Zmijewski, MA; Wortsman, J; Paus, R. (2008) Melatonin in the skin: synthesis, metabolism and functions. Trends Endocrinol. Metab., 19 (1): 17-24. [PMID:18155917]
Srinivasan, V; Pandi-Perumal, SR; Spence, DW; Moscovitch, A; Trakht, I; Brown, GM; Cardinali, DP. (2010) Potential use of melatonergic drugs in analgesia: mechanisms of action. Brain Res. Bull., 81 (4-5): 362-71. [PMID:20005925]
1. Audinot, V., Mailliet, F., Lahaye-Brasseur, C., Bonnaud, A., Le Gall, A., Amossé, C., Dromaint, S., Rodriguez, M., Nagel, N., Galizzi, J. P., Malpaux, B., Guillaumet, G., Lesieur, D., Lefoulon, F., Renard, P., Delagrange, P. and Boutin, J. A. (2003) New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol, 367: 553-561. [PMID:12764576]
2. Ayoub, MA; Levoye, A; Delagrange, P; Jockers, R. (2004) Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers. Mol. Pharmacol., 66 (2): 312-21. [PMID:15266022]
3. Browning, C., Beresford, I., Fraser, N. and Giles, H. (2000) Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors. Br. J. Pharmacol., 129: 877-886. [PMID:10696085]
4. Dubocovich, M. L., Masana, M. I., Iacob, S. and Sauri, D. M. (1997) Melatonin receptor antagonists that differentiate between the human Mel1aand Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch. Pharmacol., 355: 365-375. [PMID:9089668]
5. Dubocovich, M. L., Yun, K., Al-Ghoul, W. M., Benloucif, S. and Masana, M. I. (1998) Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J, 12: 1211-1220. [PMID:9737724]
6. Dubocovich, ML; Delagrange, P; Krause, DN; Sugden, D; Cardinali, DP; Olcese, J. (2010) International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev., 62 (3): 343-80. [PMID:20605968]
7. Dufourny, L; Levasseur, A; Migaud, M; Callebaut, I; Pontarotti, P; Malpaux, B; Monget, P. (2008) GPR50 is the mammalian ortholog of Mel1c: evidence of rapid evolution in mammals. BMC Evol. Biol., 8: 105. [PMID:18400093]
8. Eison, A. S. and Mullins, U. L. (1993) Melatonin binding sites are functionally coupled to phosphoinositide hydrolysis in Syrian hamster RPMI 1846 melanoma cells. Life Sci, 53: PL393-PL398. [PMID:8246675]
9. Faust, R., Garratt, P. J., Jones, R., Yeh, L. K., Tsotinis, A., Panoussopoulou, M., Calogeropoulou, T., Teh, M. T. and Sugden, D. (2000) Mapping the melatonin receptor. 6. Melatonin agonists and antagonists derived from 6H-isoindolo[2,1-a]indoles, 5,6-dihydroindolo[2,1-a]isoquinolines, and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles. J Med Chem, 43: 1050-1061. [PMID:10737738]
10. Kato, K., Hirai, K., Nishiyama, K., Uchikawa, O., Fukatsu, K., Ohkawa, S., Kawamata, Y., Hinuma, S. and Miyamoto, M. (2005) Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology, 48: 301-310. [PMID:15695169]
11. Lucchelli, A; Santagostino-Barbone, MG; Tonini, M. (1997) Investigation into the contractile response of melatonin in the guinea-pig isolated proximal colon: the role of 5-HT4 and melatonin receptors. Br. J. Pharmacol., 121 (8): 1775-81. [PMID:9283717]
12. Molinari, E. J., North, P. C. and Dubocovich, M. L. (1996) 2-[125I]iodo-5-methoxycarbonylamino-N-acetyltryptamine: a selective radioligand for the characterization of melatonin ML2 binding sites. Eur J Pharmacol, 301: 159-168. [PMID:8773460]
13. Nosjean, O., Ferro, M., Cogé, F., Beauverger, P., Henlin, J. M., Lefoulon, F., Fauchere, J. L., Delagrange, P., Canet, E. and Boutin, J. A. (2000) Identification of the melatonin-binding site MT3 as the quinone reductase 2. J Biol Chem, 275: 31311-31317. [PMID:10913150]
14. Nosjean, O; Nicolas, JP; Klupsch, F; Delagrange, P; Canet, E; Boutin, JA. (2001) Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2 . Biochem. Pharmacol., 61 (11): 1369-79. [PMID:11331072]
15. Pintor, J; Peláez, T; Hoyle, CH; Peral, A. (2003) Ocular hypotensive effects of melatonin receptor agonists in the rabbit: further evidence for an MT3 receptor. Br. J. Pharmacol., 138 (5): 831-6. [PMID:12642384]
16. Popova, JS; Dubocovich, ML. (1995) Melatonin receptor-mediated stimulation of phosphoinositide breakdown in chick brain slices. J. Neurochem., 64 (1): 130-8. [PMID:7798906]
17. Sugden, D; Yeh, LK; Teh, MT. (1999) Design of subtype selective melatonin receptor agonists and antagonists. Reprod. Nutr. Dev., 39 (3): 335-44. [PMID:10420436]
18. Teh, MT; Sugden, D. (1998) Comparison of the structure-activity relationships of melatonin receptor agonists and antagonists: lengthening the N-acyl side-chain has differing effects on potency on Xenopus melanophores. Naunyn Schmiedebergs Arch. Pharmacol., 358 (5): 522-8. [PMID:9840420]
19. Ting, K. N., Blaylock, N. A., Sugden, D., Delagrange, P., Scalbert, E. and Wilson, V. G. (1999) Molecular and pharmacological evidence for MT1 melatonin receptor subtype in the tail artery of juvenile Wistar rats. Br J Pharmacol, 127: 987-995. [PMID:10433507]
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melatonin, 2-iodo-melatonin, S20098 (agomelatine), GR 196429, LY 156735 and ramelteon [10] are nonselective agonists for MT1 and MT2 receptors. (-)-AMMTC displays an ∼400-fold greater agonist potency than (+)-AMMTC at rat MT1 receptors (see AMMTC for structure) [19]. luzindole is an MT1/MT2 melatonin receptor-selective competitive antagonist with some selectivity for the MT2 receptor [5]. MT1/MT2 heterodimers present different pharmacological profiles from MT1 and MT2 receptors [2].
The MT3 binding site of hamster brain and peripheral tissues such as kidney and testis, also termed the ML2 receptor, binds selectively 2-iodo-[125I]5MCA-NAT [12]. Pharmacological investigations of MT3 binding sites have primarily been conducted in hamster tissues. At this site, N-acetylserotonin [8,11-12,16] and 5MCA-NAT [16] appear to function as agonists, while prazosin [11] functions as an antagonist. A suggested physiological function of the MT3 receptor is in the control of intraocular pressure in rabbits [15]. The MT3 binding site of hamster kidney was also identified as the hamster homologue of human quinone reductase 2 (ENSG00000124588,[13-14]). Xenopus melanophores and chick brain express a distinct receptor (x420, P49219; c346, P49288, initially termed Mel1C) coupled to the Gi/o family of G proteins, for which GPR50 has recently been suggested to be a mammalian counterpart [7] although melatonin does not bind to GPR50 receptors.