Wang Q J, Adrian T E
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
Int J Pancreatol. 1995 Jun;17(3):261-9. doi: 10.1007/BF02785823.
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.
胆囊收缩素（CCK）和蛙皮素可刺激分散的胰腺腺泡产生剂量依赖性淀粉酶分泌。为确定细胞蛋白酶是否可通过降解这些调节肽来减少分泌，研究了蛋白酶抑制对CCK和蛙皮素刺激的淀粉酶分泌的影响。研究了一系列蛋白酶抑制剂，包括杆菌肽、苯甲基磺酰氟、卡托普利、贝司他汀、磷酰胺素和1,10-菲咯啉。杆菌肽（0.35 mM）显著增强了腺泡淀粉酶对CCK和蛙皮素的分泌反应，表明这两种肽被胰腺腺泡细胞的一种内肽酶降解。相反，苯甲基磺酰氟（1 mM）抑制了CCK和蛙皮素刺激的淀粉酶释放，表明其与该抑制剂以及CCK或蛙皮素受体发生了共价相互作用。其他蛋白酶抑制剂对腺泡细胞分泌的影响极小或没有影响。这些结果表明，杆菌肽是一种有价值的酶抑制剂，可增强CCK和蛙皮素对腺泡细胞的作用。相反，在使用这些促分泌剂研究胰腺功能时应避免使用苯甲基磺酰氟。
