Regulation of phosphatidylinositol 4-kinase activity in rat pancreatic acini.
Previous data showed that carbachol (CCh) elicits a concentration-dependent increase in phosphatidylinositol (PtdIns) 4-kinase activity in homogenates derived from agonist-stimulated pancreatic acini. In the present study CCh elicited a time-dependent increase in PtdIns 4-kinase activity, which was blocked by n-methylscopolamine and mimicked by muscarine. A membrane-associated PtdIns 4-kinase activity was identified that displayed maximal activity in the pH range of 5.5-8.5. The zymogen granule fraction possessed relatively high specific enzyme activity, which was sensitive to CCh stimulation. The enzyme had apparent Km values for PtdIns and ATP of 4 and 60 microM, respectively. CCh caused no discernible change in the Km for either PtdIns or ATP but increased Vmax. Dioctanoylglycerol and oleoyl acetylglycerol augmented PtdIns 4-kinase activity, which was blocked by staurosporine, thus suggesting a possible role for protein kinase C in the regulation of PtdIns 4-kinase. These collective findings demonstrate a muscarinic receptor-mediated regulation of PtdIns 4-kinase activity in exocrine pancreas, involving a protein kinase C-dependent process.
Department of Pharmacology and Therapeutics, State University of New York, Buffalo 14214.
B R
BR
Conway
M
M
Withiam-Leitch
R P
RP
Rubin
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007700:Kinetics; D009116:Muscarine / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology*; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology; D013347:Subcellular Fractions / Q000201:enzymology
D011976:Receptors, Muscarinic; D009116:Muscarine; D002217:Carbachol; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011493:Protein Kinase C