Role of cyclic AMP in prostaglandin mediated responses in the neural retina

Exogenous prostaglandin (PGs) have been shown to inhibit dopamine (DA) release from the rabbit retina via an effect on presynaptic EP ₃-receptors. In the present study, we investigated the possible involvement 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 [ ³H]DA release from isolated, superfused rabbit retinas without affecting basal tracer efflux suggesting that presynaptic cyclic AMP may be involved in the pathway leading to DA release. Forskolin attenuated inhibition of evoked [ ³H]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. Furthermore, sulprostone was more potent than PGE ₂ in attenuating forskolin-activated cyclic AMP production. The inhibition of forskolin-elevated cyclic AMP levels caused by PGE ₂ was, however, unaffected by the EP ₁-receptor antagonist, AH6809. We conclude that the regulation of DA release by presynaptic prostanoid EP ₃-receptors may be mediated, at least in part, through an inhibitory effect of adenylyl cyclase.