Melatonin receptors activate heteromeric G-protein coupled Kir3 channels.
The effects of melatonin on circadian pacemaker activity in the central nervous system may be the result of melatonin receptor activation of G-protein coupled potassium channels which inhibit the action potential firing of neurons. Xenopus laevis and human1a melatonin receptors stimulated heteromeric G-protein activated inwardly rectifying potassium channels (Kir3.1/Kir3.2) when expressed in vitro in oocytes. Pertussis toxin reduced iodo-melatonin (87.1% reduction) and melatonin (90.3% reduction) stimulated currents in a time-dependent manner for cells expressing X. laevis receptors. A similar pertussis toxin inhibition was observed for human melatonin receptors (melatonin, 78.9% reduction). This suggests a potential role for heteromeric Kir3 channels in the receptor-mediated actions of melatonin in vivo.
Nelson
C S
CS
Center for Research on Occupational and Environmental Toxicology, Oregon Health Science University, Portland 97201, USA.
Marino
J L
JL
Allen
C N
CN
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D010957:Plasmids; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D018075:RNA, Complementary / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014982:Xenopus laevis
D015221:Potassium Channels; D018075:RNA, Complementary; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D008550:Melatonin