Nicotine-induced ATP secretion from chromaffin cells was blocked by imipramine and desipramine. This blocking action took place on both, fast and slow, components of ATP secretion. Exposure of chromaffin cells to nicotine (10 μM) for 4 s induced an inward current of about -155 pA. Imipramine and desipramine blocked, in a concentration-dependent manner, both peak inward current and total charge influx in response to nicotine. In addition, imipramine and desipramine partially (40%) blocked depolarization-induced ATP secretion and Ca2+ currents evoked by high K+. This suggests that tricyclic antidepressants block nicotine-induced ATP secretion by acting on two targets: one is the nicotinic receptor itself and the second one are voltage-dependent Ca2+ channels.