A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum.

Electrical stimulation of guinea pig ileum preloaded with [3H]choline provokes the release of [3H]acetylcholine (ACh) in a Ca2+-dependent manner. This release was markedly increased by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). The combination of the ionophore A23187 and TPA produced the release of [3H]ACh up to a level equal to or exceeding a maximal response induced by electrical stimulation. A23187 alone gave only a minor response and TPA alone had no apparent effect on the [3H]ACh release. Thus, protein kinase C probably plays a role in cell surface signal transduction related to the release of transmitters from nerve endings.