Role of protein kinase C in the vesicular release of acetylcholine and norepinephrine from enteric neurons of the guinea pig small intestine.

The involvement of protein kinase C in the release of [3H]acetylcholine (ACh) and [3H]norepinephrine (NE) was studied in strips of guinea pig small intestine. 12-O-tetradecanoyl phorbol 13-acetate (TPA), but not 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) potentiated the A23187-evoked release of [3H]ACh and [3H]NE from the strips of small intestine preloaded with [3H]choline and [3H]NE, and the potentiating effect of TPA was inhibited by polymyxin B. High K+-evoked releases of [3H]ACh and [3H]NE in the presence of tetrodotoxin were also potentiated by TPA. These TPA-induced potentiations of the evoked release were greater at a low concentration of external Ca2+ (0.5 mM) than at a high concentration (2 mM). Ouabain induced the release of these neurotransmitters both in the absence and presence of the low concentration of external Ca2+. The ouabain-evoked release was not altered by TPA. These results indicate that the activation of protein kinase C potentiates the vesicular release of ACh and NE at low Ca2+ concentration from the nerve terminals of enteric neurons in the guinea pig small intestine.