Although it is suspected that dopamine (DA) inhibits a Ca++ current in sympathetic neurons, the receptor and the Ca++ channel type involved are still unknown. We found that DA caused a reversible inhibition on omega-conotoxin sensitive and resistant Ca++ currents in the superior cervical ganglion (SCG). The concentration of DA that induced half-maximal inhibition was 3.0 microM. The DA receptor agonists (+/-)-SKF-38393 (D1 type) and quinpirole (D2 type) appeared unable to induce an inhibition of the Ca++ current. Furthermore, the receptor antagonists SCH-23390 (D1 type) and (-)-sulpiride (D2 type) did not prevent the inhibitory effect of DA. This suggests that the effect of DA on the Ca++ current was not due to activation of DA receptors. The inhibition of the Ca2++ current by DA was reduced by application of 1 microM phentolamine, a nonselective alpha adrenergic antagonist, and by prazosin and yohimbine, alpha-1 and alpha-2 receptor antagonists, respectively. The beta adrenergic receptor antagonist propranolol did not block the effect of DA. A guanine nucleotide-binding protein appears to be involved in the activation of adrenergic receptors by DA. The addition of GTP-gamma-S (0.1 mM) to the intracellular solution produced an effect similar to that of DA. Incubation of sympathetic neurons with pertussis toxin reduced the effect of DA by 90%. The results indicate that DA reduces the number of available Ca++ channels in sympathetic neurons by activation of alpha adrenergic receptors, which are associated with a pertussis-sensitive GTP-binding protein.