ROLE OF CYCLIC-AMP IN PROSTAGLANDIN-MEDIATED RESPONSES IN THE NEURAL RETINA

Exogenous prostaglandins (PGs) have been shown to inhibit dopamine (DA ) release from the rabbit retina via an effect on presynaptic EP(3)-re ceptors. In the present study, we investigated the possible involvemen t of cyclic AMP in DA release and in the prostanoid receptor mediated regulation of DA release from the neural retina. Both forskolin and 8- bromo-cyclic AMP enhanced field stimulation-evoked [H-3]DA release fro m isolated, superfused rabbit retinas without affecting basal tracer e fflux suggesting that presynaptic cyclic AMP may be involved in the pa thway leading to DA release. Forskolin attenuated inhibition of evoked [H-3]DA release caused by low but not high concentrations of PGE(2). Both PGE(2) and sulprostone had no significant effect on basal cyclic AMP levels but inhibited forskolin-stimulated cyclic AMP formation. Fu rthermore, sulprostone was more potent than PGE(2) in attenuating fors kolin-activated cyclic AMP production. The inhibition of forskolin-ele vated cyclic AMP levels caused by PGE(2) was, however, unaffected by t he EP(1)-receptor antagonist, AH6809. We conclude that the regulation of DA release by presynaptic prostanoid EP(3)-receptors may be mediate d, at least in part, through an inhibitory effect on adenylyl cyclase.