Phorbol ester inhibits cholecystokinin octapeptide-induced amylase secretion and calcium mobilization, but is without effect on secretagogue-induced hydrolysis of phosphatidylinositol 4,5-bisphosphate in rabbit pancreatic acini.
The effect of prolonged protein kinase C activation on cholecystokinin octapeptide (CCK-8)-induced amylase secretion from rabbit pancreatic acini was studied by means of the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). The phorbol ester itself increased basal amylase secretion but inhibited completely the secretory response to relatively low concentrations of CCK-8. The inhibitory action of TPA on CCK-8-induced amylase secretion was paralleled by inhibition of CCK-8-induced calcium mobilization but not by inhibition of CCK-8-induced breakdown of 32P-labelled phosphatidylinositol 4,5-bisphosphate. The results presented suggest that protein kinase C, or one of its phosphorylated products, inhibits the CCK-8-stimulated pathway leading to secretion at a level beyond the secretagogue-induced hydrolysis of phosphatidylinositol 4,5-bisphosphate. Inhibition of the initial, inositol 1,4,5-trisphosphate-mediated and extracellular calcium-independent, increase in free cytosolic calcium concentration, together with the findings of others, suggests that the efficacy of this inositol-phosphate to release calcium is reduced.
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006868:Hydrolysis; D010179:Pancreas / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000681:Amylases; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium