Changes in pattern of enzyme secretion by rat pancreas during repeated trypsin inhibitor treatment.

In conscious rats with cannulated pancreatic ducts, the synthetic trypsin inhibitor camostat (400 mg/kg) was instilled into the stomach once daily on 5 consecutive days. Each camostat administration stimulated the secretion of juice, bicarbonate, and protein. From day 2 to day 5, basal protein secretion measured before the daily instillation of camostat was increased, whereas basal secretion of volume and bicarbonate remained unchanged. The secretory responses to camostat increased up to day 3 of treatment without further change on days 4 and 5. In response to acute camostat instillation, parallel secretion of enzymes was found. Within 1 day, however, a change in the composition of secreted enzymes was observed. After 3 days, the percentage of amylase in pancreatic juice decreased by approximately 50%, whereas the relative amount of proteinases and the specific activity of phospholipase A2 doubled. The alteration of protein patterns in pancreatic juice parallels the effect on enzymes stored in the gland. The results demonstrate that adaptation of enzyme secretion in the exocrine pancreas occurs after a short period of treatment with camostat. Because this compound stimulated protein, volume, and bicarbonate secretion, it is suggested that other factors in addition to cholecystokinin may be involved in this adaptation process.