FUNCTIONAL INTERACTION OF MELATONIN RECEPTORS AND D1 DOPAMINE-RECEPTORS IN CULTURED CHICK RETINAL NEURONS

The possible interaction of melatonin receptors and D1 dopamine recept ors was investigated in neural cells prepared from embryonic day 8 chi ck 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-chlo romelatonin). 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 a t all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the s timulation 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 inhi bited the response to melatonin. In contrast to its effect on cAMP acc umulation, melatonin had no effect on dopamine-stimulated inositol pho sphate accumulation, These results suggest that melatonin receptors ar e coupled to dopamine receptor-regulated adenylate cyclase via an inhi bitory G protein, and demonstrate another mechanism, in addition to in hibition of dopamine release, through which melatonin can modulate dop aminergic neurotransmission.