CARBACHOL ACTIVATES PROTEIN-KINASE-C IN DISPERSED GASTRIC CHIEF CELLS

We used an 'in situ' kinase assay to examine agonist-induced protein k inase C (PKC) activation in dispersed chief cells from guinea-pig stom ach. Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, and carba moylcholine, a cholinergic agent, caused a 4- and 3-fold increase in p epsinogen secretion from dispersed chief cells respectively. Whereas P MA caused a rapid 3-fold increase in peptide kinase activity, carbacho l caused a 15%, increase in activity that was inhibited by the PKC inh ibitor, CGP 41 251. Concentrations of carbamoylcholine and a Ca2+ iono phore that were sub-maximal for stimulation of pepsinogen secretion di d not cause PKC activation. These results indicate that, in the absenc e of PKC activation, other mechanisms, most likely involving changes i n cellular Ca2+, are sufficient to stimulate pepsinogen secretion. Nev ertheless, carbamoylcholine stimulated maximal secretion of pepsinogen only at concentrations that also resulted in activation of PKC. Moreo ver, these data indicate that relatively small increases in PKC activi ty (5-10%) can stimulate pepsinogen secretion from dispersed chief cel ls.