Dopamine (1 microM) reversibly scaled down barium current through high-voltage activated (HVA) calcium channels but had little effect on the time course of current activation in cultured frog melanotrophs. Intracellular perfusion with guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S; 100 microM) sustained the effect of dopamine. Moreover, GTP gamma S drastically slowed down the current activation kinetics. The latter effect was in part reversed by dopamine. A conditioning prepulse to +70 mV facilitated the current in GTP gamma S-dialyzed cells but not in cells exposed to dopamine. These results suggest the existence of a dual G protein-mediated mechanism for reducing HVA calcium current.