DOPAMINE-DEPENDENT CYCLIC-AMP GENERATING-SYSTEM IN CHICK RETINA AND ITS RELATION TO MELATONIN BIOSYNTHESIS

Stimulation of a (D)4-like dopamine (DA) receptors inhibits a cAMP-dep endent increase in serotonin N-acetyltransferase activity and melatoni n biosynthesis in the chick retina. In order to gain more insight into the molecular mechanisms underlying this suppressive action of DA, th e effects of selective stimulation of the D2-family of DA receptors (i ncluding the D-4-subtype) on cAMP formation were examined in chick ret ina using two experimental approaches: measurements of adenylyl cyclas e activity in retinal homogenates, and cAMP accumulation in eye cup pr eparations prelabeled with [H-3]adenine. The DA-sensitive adenylyl cyc lase system is well expressed in chick retina. DA increased both basal and forskolin-stimulated adenylyl cyclase activity. This effect of DA was antagonized by SCH 23390 (a blocker of D1-family of DA receptors) and not affected by sulpiride (a D2-family blocker). Incubation of re tinal homogenates with quinpirole (a predominant agonist of D-3/D-4 DA receptor subtypes) did not produce any major changes in adenylyl cycl ase activity. On the other hand, activation of D-4-like DA receptor su btype by quinpirole decreased forskolin-stimulated cAMP formation in i ntact chick retinas maintained in ''eye-cup'' preparations. It is sugg ested that D-4-like DA receptors regulating melatonin biosynthesis in chick retina may be indirectly linked to the cAMP generating system.