ANTAGONISM BY FORSKOLIN OF THE 5-HT3 RECEPTOR-MEDIATED CURRENT IN NODOSE GANGLION NEURONS IS INDEPENDENT OF CYCLIC-AMP

The effect of forskolin on the inward current mediated by 5-HT3 receptors (5-HT current) was investigated in rat nodose ganglion neurons. Forskolin inhibited the peak amplitude of the 5-HT current and increased current desensitization in a dose-dependent manner. Dideoxyforskolin, which does not stimulate adenylate cyclase, had a similar inhibitory effect on the 5-HT current. The effect of forskolin was neither mimicked by intracellular application of exogenous cyclic AMP (0.5 to 3 mM) nor occluded by intracellular forskolin (30 mu M) or protein kinase inhibitor H-7 (100 mu M). Intracellular applications of forskolin, cyclic AMP or H-7 had no effect on 5-HT current. Data suggest that forskolin acted at an extracellular site on 5-HT3 receptors and this effect of forskolin was not mediated by cyclic AMP-dependent processes.