MELATONIN RECEPTORS - MOLECULAR-BIOLOGY OF A NEW FAMILY OF G-PROTEIN-COUPLED RECEPTORS

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 melato nin agonist 2-[I-125]iodomelatonin (I-125-Mel). Two mammalian melatoni n receptor subtypes have been identified by molecular cloning studies. The mammalian Mel(1a) melatonin receptor is expressed in most sites c ontaining I-125-Mel binding. This includes the hypothalamic suprachias matic nucleus and hypophyseal pars tuberalis, presumed sites of the ci rcadian and some of the reproductive actions of melatonin, respectivel y. The mammalian Mel(1b) melatonin receptor is expressed in retina and brain and may mediate the reported effects of melatonin on retinal ph ysiology in some mammals. A third receptor subtype, the Mel(1c) melato nin receptor, has been cloned from zebra fish, Xenopus, and chickens b ut not from mammals. Molecular cloning of a melatonin receptor family now makes possible gene targeting to precisely determine the physiolog ical role(s) of each receptor subtype.