Differential effects of proteinase inhibitor camostat on exocrine pancreas in fed and fasted rats

Abstract

Effects of an oral dose of the synthetic trypsin inhibitor camostat on pancreatic exocrine function were examined in rats that were either fasted from 12 h before feeding camostat to the end of experiments or fed ad libitum. Camostat (100 mg/kg body wt) caused significant increases in plasma cholecystokinin bioactivity (peak 13.4 +/- 2.0 pM at 30 min for fasted rats vs. 16.6 +/- 1.7 pM at 2 h for fed rats; not significant) and pancreatic exocrine secretion. In fed rats, but not in fasted rats, significant increases in pancreatic exocrine secretion were observed again at 12 h after a single oral dose of camostat (juice flow 10.3 +/- 0.4 microliters/20 min in fasted rats vs. 175.5 +/- 17.8 microliters/20 min in fed rats; P < 0.001), although pancreatic juice flow in fed and fasted control rats was nearly the same. When the pancreata from camostat-pretreated rats were isolated and perfused, the early effects of camostat on pancreatic exocrine secretion were abolished, whereas the late effects (12 h postfeeding) in fed rats were still observed (juice flow 33.7 +/- 3.4 microliters/20 min vs. control 2.8 +/- 0.4 microliters/20 min; P < 0.001). Thus, in addition to humoral and neural factors, persistent functional changes might have occurred in the pancreas of the fed camostat-pretreated rats. These present results indicate that oral camostat induces two different effects, immediate and delayed, on pancreatic exocrine secretory function. Camostat exerts its immediate effects in both fed and fasted rats, whereas delayed effects were induced only in fed rats.