Effects of dibutyryl cyclic AMP and theophylline on rat pancreatic phospholipids in vitro Ca 2+-sensitive decrease in phosphatidylinositol and cycloheximide-sensitive increase in phosphatidic acid

Abstract

We evaluated the effects of dibutyryl cyclic AMP and theophylline on rat pancreatic phospholipid metabolism in vitro. Dibutyryl cyclic AMP decreased mean phosphatidylinositol concentration by 30%, increased phosphatidic acid and phosphatidylglycerol concentrations by 90 and 25%, respectively, and increased [ 32P]phosphate incorporation into phosphatidic acid and phosphatidylinositol several-fold. Theophylline provoked similar changes in phosphatidic acid and phosphatidylinositol concentrations, and both stimulatory agents enhanced amylase and insulin secretion. Effects of dibutyryl cyclic AMP on amylase secretion and phospholipid levels were dependent on Ca 2+. Cycloheximide blocked induced increases in phosphatidic acid, but did not diminish phosphatidyl-inositol breakdown or amylase secretion. Contrary to previous postulations, the present findings suggest: (a) cyclic AMP provokes large-scale phosphatidylinositol breakdown in the pancreas; (b) this phosphatidylinositol breakdown is dependent on Ca 2+; and (c) phosphatidylinositol breakdown may contribute to exocytosis. In addition, it appears that a labile protein is required for synthesis of phosphatidic acid from 1,2-diacylglycerol and ATP.