Copyright © by The American Society for Pharmacology and Experimental Therapeutics All rights of reproduction in any form reserved. MOLECUlAR PHARMACOLOGY, 50’.166-174 (1996). Characterization and Regulation of the Human ML1A Melatonin Receptor Stably Exp

The human ML1A melatonin receptor is expressed in the supra-chiasmatic nucleus of the hypothalamus and is believed to regulate circadian rhythms. We report the kinetic characteris-tics and pharmacological profile of 2-[125l]iodomelatonin bind-ing and the signaling pathway and agonist regulation of the human ML1A melatonin receptor stably expressed in Chinese hamster ovary cells. Association of 2-[1251]iodomelatonin bind-ing was maximal by 1.5 hr at 37#{176}and fully dissociated on the addition of 1 M melatonin. The binding of 2-[125l]iodomelatonin was saturable and of high affinity (I< = 74 ± 14 pM, Bm 679 ± 88 fmol/mg protein; three experiments). The pharmacological profile of various melatonin analogues revealed a profile (2-iodomelatonin melatonin> N-acetyl serotonin> luzindole) characteristic of an ML1 subtype. Competition of melatonin for 2-[125l]iodomelatonin binding to the human ML1A receptor i