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Melatonin Receptors: Molecular Biology of a New Family of G Protein-Coupled Receptors

Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

A family of high-affinity, G protein-coupled receptors for the pineal hormone melatonin has been cloned from vertebrates. These recombinant receptors exhibit similar affinity and pharmacological characteristics to each other and to endogenous receptors, as defined with the melatonin agonist 2-[ ¹²⁵I]iodomelatonin (¹²⁵I-Mel). Two mammalian melatonin receptor subtypes have been identified by molecular cloning studies. The mammalian Mel_1a melatonin receptor is expressed in most sites containing ¹²⁵I-Mel binding. This includes the hypothalamic suprachiasmatic nucleus and hypophyseal pars tuberalis, presumed sites of the circadian and some of the reproductive actions of melatonin, respectively. The mammalian Mel _1b melatonin receptor is expressed in retina and brain and may mediate the reported effects of melatonin on retinal physiology in some mammals. A third receptor subtype, the Mel_1c melatonin receptor, has been cloned from zebra fish, Xenopus, and chickens but not from mammals. Molecular cloning of a melatonin receptor family now makes possible gene targeting to precisely determine the physiological role(s) of each receptor subtype.

Key Words: melatonin • receptors • G protein • cyclic AMP • signal transduction • circadian rhythms

Journal of Biological Rhythms, Vol. 12, No. 6, 528-531 (1997)
DOI: 10.1177/074873049701200606


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