Melatonin receptor 1A explained

Melatonin receptor type 1A is a protein that in humans is encoded by the MTNR1A gene.^{[1] [2]}

Function

This gene encodes the MT₁ protein, one of two high-affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G protein-coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin.

Ligands

1. Melatonin – full agonist
2. Afobazole – agonist
3. Agomelatine – agonist

See also

• Melatonin receptor
• Discovery and development of melatonin receptor agonists

Further reading

• Brzezinski A . Melatonin in humans . The New England Journal of Medicine . 336 . 3 . 186–95 . Jan 1997 . 8988899 . 10.1056/NEJM199701163360306 .
• Khan AU, Olson DL . Physical therapy and exercise-induced bronchospasm . Physical Therapy . 55 . 8 . 878–81 . Aug 1975 . 1144527 . 10.1093/ptj/55.8.878.
• Reppert SM, Weaver DR, Ebisawa T . Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses . Neuron . 13 . 5 . 1177–85 . Nov 1994 . 7946354 . 10.1016/0896-6273(94)90055-8 . 19805481 .
• Witt-Enderby PA, Dubocovich ML . Characterization and regulation of the human ML1A melatonin receptor stably expressed in Chinese hamster ovary cells . Molecular Pharmacology . 50 . 1 . 166–74 . Jul 1996 . 8700109 .
• Witt-Enderby PA, Masana MI, Dubocovich ML . Physiological exposure to melatonin supersensitizes the cyclic adenosine 3',5'-monophosphate-dependent signal transduction cascade in Chinese hamster ovary cells expressing the human mt1 melatonin receptor . Endocrinology . 139 . 7 . 3064–71 . Jul 1998 . 9645677 . 10.1210/endo.139.7.6102 . free .
• Ebisawa T, Kajimura N, Uchiyama M, Katoh M, Sekimoto M, Watanabe T, Ozeki Y, Ikeda M, Jodoi T, Sugishita M, Iwase T, Kamei Y, Kim K, Shibui K, Kudo Y, Yamada N, Toyoshima R, Okawa M, Takahashi K, Yamauchi T . Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders . Biochemical and Biophysical Research Communications . 262 . 3 . 832–7 . Sep 1999 . 10471411 . 10.1006/bbrc.1999.1308 .
• Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R . Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins . Molecular Endocrinology . 13 . 12 . 2025–38 . Dec 1999 . 10598579 . 10.1210/me.13.12.2025 . free .
• Niles LP, Wang J, Shen L, Lobb DK, Younglai EV . Melatonin receptor mRNA expression in human granulosa cells . Molecular and Cellular Endocrinology . 156 . 1–2 . 107–10 . Oct 1999 . 10612428 . 10.1016/S0303-7207(99)00135-5 . 42730113 .
• Song CK, Bartness TJ . CNS sympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 281 . 2 . R666–72 . Aug 2001 . 11448873 . 10.1152/ajpregu.2001.281.2.R666. 15384503 .
• Roy D, Angelini NL, Fujieda H, Brown GM, Belsham DD . Cyclical regulation of GnRH gene expression in GT1-7 GnRH-secreting neurons by melatonin . Endocrinology . 142 . 11 . 4711–20 . Nov 2001 . 11606436 . 10.1210/en.142.11.4711 . free .
• Savaskan E, Olivieri G, Meier F, Brydon L, Jockers R, Ravid R, Wirz-Justice A, Müller-Spahn F . Increased melatonin 1a-receptor immunoreactivity in the hippocampus of Alzheimer's disease patients . Journal of Pineal Research . 32 . 1 . 59–62 . Jan 2002 . 11841602 . 10.1034/j.1600-079x.2002.00841.x . 37172611 .
• Savaskan E, Wirz-Justice A, Olivieri G, Pache M, Kräuchi K, Brydon L, Jockers R, Müller-Spahn F, Meyer P . Distribution of melatonin MT1 receptor immunoreactivity in human retina . The Journal of Histochemistry and Cytochemistry . 50 . 4 . 519–26 . Apr 2002 . 11897804 . 10.1177/002215540205000408 . free .
• Ayoub MA, Couturier C, Lucas-Meunier E, Angers S, Fossier P, Bouvier M, Jockers R . Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer . The Journal of Biological Chemistry . 277 . 24 . 21522–8 . Jun 2002 . 11940583 . 10.1074/jbc.M200729200 . free .
• Yuan L, Collins AR, Dai J, Dubocovich ML, Hill SM . MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells . Molecular and Cellular Endocrinology . 192 . 1–2 . 147–56 . Jun 2002 . 12088876 . 10.1016/S0303-7207(02)00029-1 . 54393974 .
• Slominski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J . Functional activity of serotoninergic and melatoninergic systems expressed in the skin . Journal of Cellular Physiology . 196 . 1 . 144–53 . Jul 2003 . 12767050 . 10.1002/jcp.10287 . 24534729 . free .
• Morcuende JA, Minhas R, Dolan L, Stevens J, Beck J, Wang K, Weinstein SL, Sheffield V . Allelic variants of human melatonin 1A receptor in patients with familial adolescent idiopathic scoliosis . Spine . 28 . 17 . 2025–8; discussion 2029 . Sep 2003 . 12973153 . 10.1097/01.BRS.0000083235.74593.49 . 22201689 .
• Aust S, Thalhammer T, Humpeler S, Jäger W, Klimpfinger M, Tucek G, Obrist P, Marktl W, Penner E, Ekmekcioglu C . The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia . Journal of Pineal Research . 36 . 1 . 43–8 . Jan 2004 . 14675129 . 10.1046/j.1600-079X.2003.00095.x . 25934742 . free .

Notes and References

1. Slaugenhaupt SA, Roca AL, Liebert CB, Altherr MR, Gusella JF, Reppert SM . Mapping of the gene for the Mel1a-melatonin receptor to human chromosome 4 (MTNR1A) and mouse chromosome 8 (Mtnr1a) . Genomics . 27 . 2 . 355–7 . May 1995 . 7558006 . 10.1006/geno.1995.1056 .
2. Web site: Entrez Gene: MTNR1A melatonin receptor 1A.