Role of Protein Kinase C in the Vesicular Release of Acetylcholine and Norepinephrine from Enteric Neurons of the Guinea Pig Small Intestine

Abstract

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 4α-phorbol-12, 13-didecanoate (4α-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.