Two mechanisms of inhibition by bile on luminal feedback regulation of rat pancreas

Abstract

Background: Pancreatic exocrine secretion in conscious rats is regulated by luminal protease activities. A decrease in protease activities results in pancreatic hypersecretion (luminal feedback regulation). Although bile has been known to affect this regulation, the mechanism is not clear. In the present study, the effect of bile in the intestinal lumen on luminal feedback regulation was examined. Methods: Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. Because the rate of enzyme secretion varies in individual rats, porcine trypsin was infused instead of pancreatic juice. Graded doses of porcine trypsin were infused with bile or Tris buffer containing 10 mmol/L CaCl2 instead of bile. Results: The trypsin activities in the proximal quarter of the small intestine were similar in rats infused with bile and with Tris buffer containing 10 mmol/L CaCl2 (without bile); however, increments of pancreatic secretions of fluid and protein were significantly higher in rats without bile infusion than in those with bile infusion. Infusion of calcium-free Tris buffer resulted in significantly lower trypsin activity. Conclusions: The results indicate that bile has two inhibitory mechanisms on pancreatic secretion, one stabilizing luminal trypsin, the other independent of luminal trypsin activity.