title: Effect of protease inhibitors on peptide-stimulated amylase secretion from dispersed pancreatic acini.
abstract: Cholecystokinin (CCK) and bombesin stimulate dose-dependent amylase secretion from dispersed pancreatic acini. To establish whether cellular proteases can reduce secretion by degrading these regulatory peptides, the effect of protease inhibition on CCK and bombesin stimulated amylase secretion was investigated. A spectrum of protease inhibitors, including bacitracin, phenylmethylsulfonylfluoride, captopril, bestatin, phosphoramidon, and 1,10-phenanthroline, were investigated. Bacitracin (0.35 mM) increased the acinar amylase secretory response to CCK and bombesin substantially, suggesting that these two peptides are degraded by an endopeptidase from pancreatic acinar cells. In contrast, PMSF (1 mM) inhibited CCK and bombesin stimulated amylase release, suggesting a covalent interaction with this inhibitor and CCK or bombesin receptors. Other protease inhibitors either had minimal or no effects on acinar cell secretion. These results suggest bacitracin is a valuable enzyme inhibitor that can potentiate the effect of CCK and bombesin on acinar cells. In contrast, PMSF should be avoided when using these secretagogs to study pancreatic function.
authors.affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Wang
authors.forename: T E
authors.initials: TE
authors.lastname: Adrian
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D006168:Guinea Pigs; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D010664:Phenylmethylsulfonyl Fluoride; D002766:Cholecystokinin; D000681:Amylases; D001839:Bombesin