| Description: |
Melatonin is a naturally occurring compound found in animals, plants, and microbes [, ]. In animals melatonin is secreted by the pineal gland during darkness [, ]. It regulates a variety of neuroendocrine functions and is thought to play an essential role in circadian rhythms []. Drugs that modify the action of melatonin, and hence influence circadian cycles, are of clinical interest for example, in the treatment of jet-lag []. Many of the biological effects of melatonin are produced through the activation of melatonin receptors [], which are members of rhodopsin-like G protein-coupled receptor family. There are three melatonin receptor subtypes. Melatonin receptor type 1A and melatonin receptor type 1B are present in humans and other mammals []while melatonin receptor type 1C has been identified in amphibia and birds []. There is also a closely-related orphan receptor, termed melatonin-related receptor type 1X (also known as GPR50) [], is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature. Melatonin receptor type 1C receptors are 80% identical and are distinct from 1A and 1B subtypes. Similar ligand binding and functional characteristics are observed in expressed 1A and 1C receptors. The melatonin receptors inhibit adenylyl cyclase via a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class. Melatonin receptor 1A, also known as MT1 melatonin receptor [], mediates the circadian and reproductive effects of the hormone melatonin. Melatonin receptor 1A is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal pars tuberalis [, , ].Melatonin receptor type 1B is found primarily in the retina, selected brain regions and some arterial beds [, , , , , ]. Activation of human recombinant melatonin receptor 1B inhibits the adenylyl cyclase pathway and cyclic guanosine monophosphate formation [, , ]. It is thought to participate in the circadian timing system [], inhibition of dopamine release in the retina [], and in vasodilation of the caudal artery [, ]. |
