Inhibitory effects of calmodulin antagonists on plasma membrane cyclases in Tetrahymena: calmodulin-dependent guanylate cyclase and calmodulin-independent adenylate cyclase.
Trifluoperazine was shown previously to inhibit the activation of Tetrahymena guanylate cyclase activity by calmodulin [S. Nagao, S. Kudo and Y Nozawa, Biochem. Pharmac. 19, 2709 (1981)]. The present paper reports that N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), another representative calmodulin inhibitor, inhibited the calmodulin-induced activation of the guanylate cyclase, and that trifluoperazine and W-7 also inhibited Tetrahymena adenylate cyclase. The adenylate cyclase activity was found to be present in a membrane-bound form and not to be influenced by calmodulin. The inhibitions of the adenylate cyclase activity by these agents were dose-dependent and not Ca2+-dependent. These findings suggest that the inhibitory actions of these drugs may not necessarily be specific for calmodulin-dependent enzymes in T. pyriformis.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007700:Kinetics; D013449:Sulfonamides / Q000494:pharmacology; D013769:Tetrahymena pyriformis / Q000201:enzymology*; D014268:Trifluoperazine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014150:Antipsychotic Agents; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D013449:Sulfonamides; D014665:Vasodilator Agents; D014268:Trifluoperazine; D004533:Egtazic Acid; C017967:W 7; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D002118:Calcium; D002746:Chlorpromazine