Experiments were conducted to determine the relationship between the percentage of pancreatic secretion diverted from the intestine and pancreatic exocrine secretion in conscious rats. Rats with cannulas draining bile and pancreatic juice had increasing percentages (0%-100%) of their pancreatic secretion diverted from the intestine while all bile was returned. Stimulation of pancreatic protein and fluid output by diversion of pancreatic juice from the intestine did not occur if 10% of the volume of pancreatic juice secreted was returned to the intestine. Return of 5% of pancreatic secretion reduced the pancreatic protein response by half (compared with complete diversion). The results are interpreted as evidence for a threshold in negative feedback regulation by luminal proteases whereby increased pancreatic secretion does not occur until luminal protease activity is reduced by >90%. The results also suggest that inhibition of pancreatic secretion by proteases in pancreatic juice is far more effective than inhibition by proteases (e.g., trypsin) infused singly.
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