GASTRIN DOES NOT STIMULATE GROWTH OF THE RAT PANCREAS

Background: Gastrin is thought to stimulate growth of the pancreas via gastrin/cholecystokinin (CCK)-B-type receptors. The aim of the presen t study was to examine the trophic response of the pancreas to exogeno us gastrin or to hypergastrinemia of endogenous origin and to hypogast rinemia with or without concomitant hyperCCKemia. Methods: Hypergastri nemia was induced in male Sprague-Dawley rats by continuous infusion o f human Leu(15)-gastrin-17 (5 nmol/kg/h, subcutaneously), by removal o f the acid-producing part of the stomach (fundectomy), or by treatment with omoprazole (400 mu mol/kg/day, orally). Hypogastrinemia was indu ced by antrectomy or by gastrectomy. HyperCCKemia was induced by pancr eaticobiliary diversion (PBD). The rats were killed 10 days or 8 weeks after the operations or treatments. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The pancreatic wei ght and DNA content were determined. Results: Gastrin infusion, omepra zole treatment, and fundectomy greatly increased the serum gastrin con centration. The resulting levels were very similar in the three groups and probably represent the maximum attainable physiologic serum gastr in concentration. Whereas gastrin infusion or omeprazole treatment (hy pergastrinemia) and antrectomy (hypogastrinemia) were without effect o n the weight and DNA content of the pancreas, gastrectomy (hypogastrin emia) and fundectomy (hypergastrinemia) increased the weight and DNA c ontent. PBD (hyperCCKemia) greatly increased the weight and DNA conten t of the pancreas. PBD plus fundectomy, PBD plus gastrectomy, PBD plus antrectomy, and PBD plus omeprazole increased the weight and DNA cont ent of the pancreas, as did PBD alone. Conclusion: CCK: is a physiolog ically important trophic stimulus for the rat pancreas, but gastrin is not. The increase in pancreatic weight and DNA content after fundecto my and gastrectomy cannot be explained by means of either gastrin or C CK.