Effect of protein kinase C on amylase secretion and cyclic AMP production in rat pancreatic acinar cells.

The authors examined the effects of protein kinase C on secretin-induced amylase release and cyclic AMP production in rat pancreatic acinar cells. Secretin (10(-6) M) and 12-O-tetradecanoyl-phorbol 13-acetate (TPA) (10(-6) M) induced 53% and 60% increase of amylase release from the basal level, respectively during 10 min. Simultaneous addition of TPA and secretin resulted in 42% amylase release from the basal level for 10 min. Suppression of secretin-induced amylase release was evident within 5 min of pretreatment with TPA. TPA showed the same effect on cyclic AMP production; secretin-induced increase of cyclic AMP was suppressed by pretreatment of TPA for 5 min. To explore the mechanism by which TPA inhibits secretin-induced cyclic AMP production, we also examined the effects of protein kinase C purified from rat brain on adenylate cyclase activity in pancreatic acinar membranes. Basal, forskolin- and secretin plus guanosine 5'-[gamma-thio]trisphosphate-stimulated adenylate cyclase activity were inhibited by protein kinase C in the presence of Ca++. These results suggest that protein kinase C might have a role in the inhibitory effect on adenylate cyclase in exocrine pancreas.