Inhibition by phenothiazine derivatives of the adenylate cyclase of amphibian oocytes

Abstract

The adenylate cyclase activity of membranes of Xenopus laevis oocytes and follicle cells was affected by the presence of 2-chloro-10-(3-aminopropyl)phenothiazine (CAPP) and two other antipsychotic drugs, fluphenazine and penfluridol. CAPP, at concentrations of 10 and 100 μM, had opposite effects on the activation of the oocyte adenylate cyclase by effectors that act through the G/F regulatory subunit. Under these conditions, the drug stimulated the activation by fluoride and drastically inhibited the activation by guanyl-5′-yl-imidodiphosphate [Gpp(NH)p] and by cholera toxin and GTP. The activity of the catalytic subunit measured in the presence of either Mn2- or forskolin was not affected by 100 μM CAPP. however, concentrations of this drug above 100 μM inhibited the adenylate cyclase activated by fluoride or by forskolin and also inhibited the activity of a calmodulin-independent cyclic nucleotide phosphodiesterase present in the same oocyte membrane preparation. Oocyte adenylate cyc