Effect of Cholecystokinin-A Receptor Antagonist on Rat Pancreas after Partial Pancreatectomy

Our previous study indicated that the acinar cells regenerated actively in the rat pancreatic remnant after partial (90%) pancreatectomy. On that occasion, a twofold higher mitotic activity was observed in the cells of paraduodenal than those of the medial and stump regions (regional difference). Since cholecystokinin (CCK) has been known to have various physiological functions in the digestive system, especially in the pancreas, through the CCK-A receptor, we determined the effect of a CCK-A receptor competitive antagonist (CCK-RA) (SR27897B) on pancreatic regeneration after pancreatectomy. A group of Wistar rats was administered 1 mg/kg CCK-RA twice daily for 5 days. On the 2nd day of administration, partial pancreatectomy was performed. Proliferation activity of both exocrine and endocrine cells was found to be enhanced uniformly 5 days after the pancreatectomy, and the effect was inhibited by CCK-RA. Plasma CCK level was increased by 90% pancreatectomy and decreased by CCK-RA. CCK was hypothesized to be an important factor of pancreatic exocrine and endocrine regeneration. Administration with CCK-RA suppressed mitotic activity uniformly in the three regions of paraduodenal, medial and stump. From the evidence, it was presumed that regional difference in regeneration was produced not by paracrine factor from the duodenum but by some other unknown mechanism including anatomical difference in vascular and autonomic nervous system.