The action of psychotropic drugs on adenylate cyclases and phosphodiesterases in the rat retina.

In this overview we demonstrate differences in the mode of action of DA and NA on cAMP-synthesizing systems by using psychotropic compounds such as fluphenazine and haloperidol. Evidence exists that this catecholamine induced cAMP-synthesis occurs in post-synaptic receptor-coupled adenylate cyclases. Our results reveal the expected inhibitory action of the psychotropic drugs on the DA- and NA-stimulated adenylate cyclases. We present, however, also evidence for a drug-induced inhibition of the phosphodiesterase activity involved in the NA-induced cAMP synthesis. This drug-induced inhibition of P.D.-ases was not found in the DA-governed enzymatic process. We also measured the DA- and NA-responses at various low potassium-ion concentrations (0-6 mM). Our data on this point suggest a specific membrane conformation modulated by potassium ions, which change the readiness of DA- and NA-receptors to accept the catecholamines involved. An elevation of the potassium-ion concentration up till 15 mM produced a relatively high cAMP-formation, which was suppressed by various amounts of psychotropic compounds. Our results point to different cell types in the rat retina, all containing the structure for cAMP-synthesis and cAMP-breakdown.