title: Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons.
abstract: The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2-iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine-stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation. These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322-3090.
authors.forename: P M
authors.initials: PM
authors.lastname: Iuvone
authors.forename: J
authors.initials: J
authors.lastname: Gan
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D044094:Receptors, Melatonin; D012160:Retina / Q000196:embryology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D001552:Benzazepines; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D017447:Receptors, Dopamine D1; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; C024100:6-chloromelatonin; C071262:SK&F 82958; C044556:2-iodomelatonin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D006220:Haloperidol; D008550:Melatonin; D015056:1-Methyl-3-isobutylxanthine