EFFECTS OF ENDOGENOUS AND EXOGENOUS CHOLECYSTOKININ AND OF INFUSION WITH THE CHOLECYSTOKININ ANTAGONIST L-364,718 ON PANCREATIC AND GASTROINTESTINAL GROWTH

Continuous subcutaneous infusion of cholecystokinin (CCK-8; 5 μg/kg/h) to rats for 7 weeks raised the plasma CCK concentration almost fivefold and increased the pancreatic weight by about 50 % but was without effect on the gastrointestinal tract. Continuous subcutaneous infusion of the CCK antagonist L-364,718 (200 μg/kg/h) for 7 weeks reduced the weight of the pancreas by about 30 % but was without effect on the gastrointestinal tract. The effect of continuous subcutaneous infusion of CCK-8 and L-364,718 in combination was very similar to that of L-364,718 alone. Pancreaticobiliary diversion (PBD) induced a nearly 10-fold increase in the plasma CCK concentration 3 and 7 weeks after the operation. The serum gastrin values were unaffected. The weight of the pancreas was more than doubled after 7 weeks. At the same time the small intestine had gained weight, but the colon was unaffected. Continuous subcutaneous infusion of L-364,718 prevented the effect of PBD on the pancreas. On the basis of the assumption that L-364,718 is a specific antagonist of CCK, we conclude that endogenous CCK has a trophic effect on the pancreas but not on the gastrointestinal tract and that it is essential for normal pancreatic growth. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.