ROLE OF PROTEIN-KINASE-C IN THE RELEASE OF [H-3]ACETYLCHOLINE FROM MYENTERIC PLEXUS TREATED WITH VESAMICOL

The present experiments investigated the release of [3H]acetylcholine ([H-3]ACh) from the guinea pig myenteric plexus treated with 2-(4-phen ylpiperidino)cyclohexanol (vesamicol), a drug that impairs ACh accumul ation by synaptic vesicles. Ouabain, an Na+-K+ ATPase inhibitor, relea sed [3H]ACh synthesised in the presence of (-)-vesamicol, while electr ical field stimulation or KCl depolarisation were not effective to rel ease the transmitter in this condition. The effect of ouabain was Ca2-dependent and in the presence of (-)-vesamicol it was blocked by calp hostin C, an inhibitor of protein kinase C (PKC). In addition, stimula tion of kinase C activity by a phorbol ester, but not by its inactive isomer, prevented (-)-vesamicol from interfering with the release of [ H-3]ACh in electrically-stimulated myenteric plexus, similar to the ef fect of ouabain. We conclude that release of [H-3]ACh induced by ouaba in in the presence of (-)-vesamicol depends on PKC activation. (C) 199 8 Published by Elsevier Science Ireland Ltd.