DISCREPANCY BETWEEN PANCREATIC PROTEIN SECRETION AND CCK RELEASE IN RESPONSE TO BILE-PANCREATIC JUICE DIVERSION IN THE HYPERTROPHIED RAT PANCREAS INDUCED BY SYNTHETIC TRYPSIN INHIBITOR

Abstract

Pancreatic exocrine secretion in conscious rats is mainly regulated by protease activities in the proximal intestine (luminal feedback regulation).1 Decrease in protease activities by ingestion of trypsin inhibitors (TI)s or diversion of bile-pancreatic juice (BPJ) stimulates pancreatic secretion2 and produces pancreatic hypertrophy via CCK release. Since CCK releasing factor, LCRF was purified from rat intestine,3 we determined whether the levels of LCRF, CCK, and protein secretion were synchronized to one another. Changes in pancreatic secretion, plasma CCK levels, and luminal LCRF contents produced by 2- and 4-h BPJ diversion, were determined in rats with 7-day TI treatment, and compared with controls. A diet containing 0.1% synthetic TI (ONO-3402) and a standard diet (CE-2) were fed in Wistar male rats for 7 days. After 7 day-treatment, the pancreatic wet weight was significantly higher in TI treated rats than the controls. For the experiments, on the third day of the feeding, rats were prepared with cannulas draining BPJ separately, and with a duodenal cannula and with an external jugular vein cannula. On the 7th day of the feeding, after 90 min of basal secretion with returning BPJ, BPJ were diverted. Changes in pancreatic secretions of fluid and protein were determined. After 2- and 4-h BPJ diversion, rats were sacrificed. Samples of 3-4 ml of blood were withdrawn through the venous cannula to measure plasma CCK concentrations. The proximal quarter of the small intestine was removed to measure LCRF content. The levels of LCRF and CCK were parallel (Fig. 1). Pancreatic protein secretion was higher in rats treated with TI than in controls throughout the experimental period. The plasma CCK and luminal LCRF content 4-h after BPJD was significantly lower in rats treated with TI than in controls. The hypertrophied pancreas may require a smaller dose of CCK to increase protein secretion.FIGURE 1: Changes in plasma CCK concentrations, LCRF content, and pancreatic protein secretion after 4-h BPJ diversion. *significantly different from the control values. TI; trypsin inhibitor. The numbers in the parentheses are the number of animals.