Cholinergic attenuation of the electrophysiological effects of forskolin.

Isoproterenol activates adenylate cyclase indirectly via the beta-receptors. Forskolin, on the other hand, directly activates the adenylate cyclase. Both compounds can induce slow action potentials (APs) in isolated guinea pig papillary muscles, consistent with their ability to activate adenylate cyclase. Acetylcholine (ACh), 1-10 microM, depressed or abolished slow APs induced by isoproterenol or forskolin. There was no difference between the forskolin- and isoproterenol-induced slow APs with regard to their sensitivity to ACh. Similar results were obtained in cultured embryonic chick heart cells. We conclude that forskolin induces slow APs that are essentially the same as those induced by isoproterenol, and that ACh action on depressing slow APs must be either directly on the adenylate cyclase complex and/or on another step entirely (e.g., mediated through increased cGMP.