Role of secretin in negative feedback regulation of postprandial pancreatic secretion in dogs

Abstract

Background: A negative feedback regulation of pancreatic exocrine secretion has been observed in fasting rats, pigs, and humans, but this phenomenon could not be found in fasting dogs. The aims of the present study were to investigate whether or not postprandial pancreatic secretion is regulated by a negative feedback mechanism and to determine if the mechanism is mediated by secretion and/or cholecystokinin (CCK) in dogs. Methods: In eight dogs prepared with gastric and Herrera's pancreatic cannulas, pancreatic juice was collected for 3 hours after feeding a mixed meal to measure volume, bicarbonate, and trypsin output. Peripheral venous blood was obtained to determine plasma immunoreactive secretin and CCK levels. Four groups of experiments were performed while pancreatic juice was diverted from the duodenum: (1) diversion of pancreatic juice alone, (2) intraduodenal infusion of fresh pancreatic juice while pancreatic juice was diverted, (3) intraduodenal infusion of 150 mg/h of trypsin and 300 mg/h of chymotrypsin, and (4) intraduodenal infusion of 0.1 mol/L NaHCO3. Results: Pancreatic secretion during diversion of pancreatic juice was significantly greater than that obtained while pancreatic juice was returned. Diversion-induced pancreatic hypersecretion was significantly suppressed by intraduodenal administration of pancreatic proteases, but it was not influenced significantly by 0.1 mol/L NaHCO3. The suppression by either pancreatic juice or proteases paralleled the decrease in plasma secretin response, whereas the CCK response remained unchanged. The inhibitory effect of pancreatic proteases on pancreatic secretion was blocked by a physiological dose of exogenous secretin, 0.06 clinical U · kg−1 · h−1. Conclusions: In dogs, postprandial pancreatic secretion is controlled by a negative feedback mechanism mediated mainly by the release of secretin, but not by CCK.