Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion

Bile from the liver and enzymes from the pancreas are both transported via the common bile duct to the small intestine, where they are integral in the digestion of foods, particularly fats. In experimental or therapeutic situations where the secretions from either one of these organs is diverted to a more distal region of the intestine, intestinal and pancreatic growth result. The pancreatic growth is thought to be stimulated by excessive release of the pancreatic hormone cholecystokinin. The increased growth of the pancreas and may presage future adverse occurrences such as pancreatitis (inflammation of the pancreas) and malignant pancreatic tumors. To determine the effects of a pharmacological antagonist of cholecystokinin (CCK) on pancreatic growth, a study was carried out with male rats that were subjected to either pancreaticobiliary diversion (PBD; accomplished by transplanting a section of the lower intestine to the area between the stomach and initial small intestine) or a sham operation. Half of the animals in each group were given a potent CCK antagonist (CR-1409). PBD resulted in a 91 and 137 percent increase in blood levels of CCK at 7 and 14 days, respectively, after the operation. The weight of the pancreas was significantly increased by PBD, and there were numerous biochemical and functional indices of cell proliferation (such as increased RNA content, incorporation of radioactive bromodeoxyuridine, and cell birth rate). Administration of CR-1409 completely abolished the increase in pancreatic weight and cell birth rate, while having no effect on blood levels of CCK. Hence, the effect of CR-1409 is likely due to its ability to block the CCK receptor. (Consumer Summary produced by Reliance Medical Information, Inc.)