Haggblad_1987_Naunyn.Schmiedebergs.Arch.Pharmacol_336_381

Forskolin, a commonly used adenylate cyclase activator, was found to inhibit reversibly the carbachol-induced ion-translocating capacity of the nicotinic acetylcholine receptor (nAChR) on chick myotubes in a dose- (IC50 = 20 microM) and time-dependent manner. This effect was not correlated to increases in cellular cAMP. Forskolin, at a concentration (50 microM) that totally blocked the carbachol-induced 86Rb influx, caused no change in carbachol or alpha-bungarotoxin binding to chick myotube nAChR in situ. In contrast, in the presence of carbachol, forskolin inhibited (IC50 = 10 microM) the binding of 3H-phencyclidine, a putative nAChR ion-channel ligand, to Torpedo microsac nAChR. Inhibition of 3H-phencyclidine binding in the absence of carbachol was not complete. Membrane leakage studies on myotubes, measuring 3H-efflux from 2-deoxy-D(1-3H)-glucose loaded cells and electrophysiological measurements of membrane properties supported the interpretation that forskolin induced decreases in plasma membrane permeability. In conclusion, forskolin blocks the carbachol-mediated increase in permeability of the nAChR channel by (1) binding to the ion-channel (open state) and (2) generally perturbing the plasma membrane function possibly by interfering with the protein-lipid interface.