Potential mediation of somatostatin secretion from canine fundic D-cells by protein kinase c.

We examined the possible importance of protein kinase c-dependent mechanisms in mediating the stimulatory effects of gastrin and cholecystokinin (CCK) on the release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D-cells. Diacylglycerides, presumably the products of phosphoinositide breakdown that activate protein kinase c, and phospholipase C, which catalyzes the production of endogenous diacylglycerides from membrane phospholipids, both stimulated SLI secretion in a dose-dependent fashion. Both classes of agents potentiated the actions of adenosine 3',5'-cyclic monophosphate-dependent agonists but not those of gastrin and CCK. The stimulatory effects of gastrin and CCK correlated with their abilities to enhance the incorporation of 32P into membrane phosphatidyl inositol and phosphatidic acid and promote the release of [3H]inositol trisphosphate from prelabeled D-cells, two parameters of phosphoinositide turnover. These data suggest that protein kinase c may serve to transduce the signals activated by gastrin and CCK in D-cells.