Acetylcholine release from guinea pig caudate slices evoked by phorbol ester and calcium.

In guinea pig caudate slices preloaded with [3H]choline, superfusion with medium containing Ca2+ and the phorbol ester TPA (12-O-tetradecanoyl phorbol 13-acetate) produced an increase in the Ca2+-dependent, depolarization-evoked release of acetylcholine (ACh), with no significant effect on the evoked Ca2+ influx. The effect of TPA was antagonized by polymyxin B and H-7, both inhibitors of protein kinase C. The combination of TPA and calcium ionophore (A23187) provoked the release of ACh to a level equal to the maximal response induced by depolarizing stimuli. TPA alone had no significant effect on the release of ACh. These results suggest that protein kinase C probably plays a role in transmembrane signal transduction involved in the release of neurotransmitter from nerve terminals in the brain.