INFLUENCE OF EXOGENOUS APPLICATION OF PANCREATIC EXTRACTS ON ENDOGENOUS PANCREATIC-ENZYME SECRETION

The existence of negative feedback inhibition of human pancreatic enzyme secretion by proteases is controversially discussed. We have recently demonstrated that jejunal application of porcine pancreatic extracts, in a dose commonly used to treat digestive insufficiency, stimulated rather than inhibited, human pancreatic enzyme secretion. We have now studied the influence of duodenal application of high concentrations of either pure trypsin or porcine pancreatic extracts with trypsin-equivalent activity, on human pancreatic enzyme secretion. Twenty-three male volunteers were intubated with a gastric tube and a two-lumen jejunal tube to collect secretions separately via the first and third tubes and to perfuse either pure trypsin or porcine pancreatic extracts distal to the pylorus via the second tube. PEG-4.000 was continuously perfused via the second tube to correct for losses of volume. Volunteers received PEG alone during the first hour, phenylalanine during the second, PEG alone again during the third, and either phenylalanine together with trypsin or porcine pancreatic extracts during the fourth h. Activities of lipase, amylase, and chymotrypsin were measured in 15-min fractions. In addition, human lipase secretion was measured with an enzyme immunoassay, which does not crossreact with porcine lipase. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay, which utilizes amylase release by isolated rat pancreatic acini. Perfusion of the duodenum with phenylalanine caused a statistically significant stimulation of enzyme secretion. This stimulation could be inhibited by high concentrations of pure trypsin. In contrast, application of porcine pancreatic extracts, which contained the equivalent activity of trypsin, caused further increases of lipase secretion when compared to phenylalanine alone. With regards to CCK, phenylalanine led to slightly higher plasma CCK values in comparison to PEG, which were reversed by perfusion with pure trypsin. In contrast, pancreatic extracts caused significant increases in plasma CCK. This suggests that negative feedback inhibition of human pancreatic enzyme secretion can be demonstrated during perfusion of the duodenum, with pure and very high concentrations of trypsin. However, application of a mixture of porcine pancreatic enzymes, despite its high concentrations of active proteases, stimulated pancreatic secretion. We may conclude, therefore, that human pancreatic secretion cannot be inhibited by treatment with porcine pancreatic extracts.