Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin-stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.

In the present study pancreatic secretion and plasma cholecystokinin (CCK) levels were analyzed in eight volunteers after daily ingestion of the serine protease inhibitor camostate for 5 days. This was compared with the effect of a single intraduodenal dose of camostate. Prolonged administration of camostate for 5 days had no effect on basal and stimulated pancreatic secretion and plasma CCK. A single dose of camostate completely inhibited enzymatic activity of trypsin and chymotrypsin and stimulated volume, amylase, and lipase secretion but induced an only slight and insignificant increase in plasma CCK. After the ingestion of a test meal, camostate did not influence stimulated enzyme secretion and increased plasma CCK. We concluded that the intraduodenal perfusion of camostate stimulated pancreatic secretion by a feedback mechanism that is not mediated by CCK. The repeated oral administration of camostate did not induce adaptive changes in pancreatic secretion.