Calcium mobilization and protein kinase C activation are required for cholecystokinin stimulation of pancreatic cholesterol esterase secretion.
The bile salt-stimulated cholesterol esterase is a digestive enzyme synthesized by the acinar cells of the pancreas. Previous results have shown that cholesterol esterase biosynthesis and secretion in the AR42J pancreatoma cells could be increased 3-5-fold by intestinal hormones such as cholecystokinin (CCK). The purpose of the current study is to explore the signalling mechanism by which CCK stimulation of AR42J cells results in increased biosynthesis and secretion of the cholesterol esterase. The results showed that the CCK-induced cholesterol esterase secretion could be mimicked by addition of the Ca2+ ionophore A23187 or by transient incubation of AR42J cells with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). Cholesterol esterase stimulation by CCK, A23187 and PMA could be abolished by the calcium chelator BAPTA or by specific protein kinase C inhibitors such as chelerythrine. Additionally, prolonged incubation of AR42J cells with PMA to reduce the protein kinase C level, also reduced CCK-stimulated cholesterol esterase secretion to a level similar to that observed in control cells. Taken together, these data suggested that CCK activation of cholesterol esterase secretion may be mediated by a Ca(2+)-dependent protein kinase C pathway, requiring increases in calcium mobilization and activation of protein kinase C.
Brodt-Eppley
J
J
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529.
Hui
D Y
DY
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology*; D010190:Pancreatic Neoplasms; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D002787:Sterol Esterase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000001:Calcimycin; D004533:Egtazic Acid; D002766:Cholecystokinin; D011493:Protein Kinase C; D002787:Sterol Esterase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium