Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses.
The pineal hormone melatonin regulates seasonal reproductive function and modulates circadian rhythms in mammals. We now report the cloning and characterization of a high affinity receptor for melatonin from the sheep and human. The receptor cDNAs encode proteins that are members of a newly discovered group within the G protein-coupled receptor family. Expression of the sheep and human receptors in COS-7 cells results in high affinity 2-[125I]iodomelatonin binding and pharmacological characteristics similar to endogenous high affinity receptors. Functional studies of NIH 3T3 cells stably expressing the sheep receptor show that the mammalian melatonin receptor is coupled to inhibition of adenylyl cyclase through a pertussis toxin-sensitive mechanism. In situ hybridization studies of melatonin receptor mRNA in several mammals reveal hybridization signals in the hypophyseal pars tuberalis and hypothalamic suprachiasmatic nucleus. The cloned high affinity receptor likely mediates the reproductive and circadian actions of melatonin in mammals.
Reppert
S M
SM
Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Weaver
D R
DR
Ebisawa
T
T
D000818:Animals; D003001:Cloning, Molecular; D016384:Consensus Sequence; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D044094:Receptors, Melatonin; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014982:Xenopus laevis
D018076:DNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D044094:Receptors, Melatonin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D008550:Melatonin