Regulation of digestive organ. An experimental study on the role of CCK, Bile and EGF

Abstract: Cholecystokinin (CCK) is known to exert secretory and trophic effects on the pancreas. Its release from the intestinal mucosa is regulated by pancresic proteases in the small intestine. However, knowledge about the type of responding exocrine cells and the time course of events during stimulation with CCK is lacking. Further, the role of CCK in the regulation of growth in other digestive organs is not known. Epidermal growth factor (EGF), which under some circumstances interacts with CCK, is found in high concentrations in the pancreas and salivary glands but information of the mitogenic effect in these organs is missing. By performing cholecystectomy, diverting bile by pancreatico-biliary diversion (PBD) or biliodigestive shunt (BDS) to the middle of the small intestine, or by giving total parenteral nutrition (TPN) the effect on plasma CCK and digestive organ growth following altered bile and enzyme flow and enteral nutrition, respectively, were studied. The time course of mitogenic effects of infusion of CCK-85, the CCK-A receptor antagonist devazepide and EGF, respectivley, were studied in the exocrine pancreas, salivary glands, liver and bilary ducts. Absence of bile in the upper small intestine, but not altered bile flow, evoked endogenous hyperCCKemia with ensuing pancreatic growth, whereas the liver and gatrointestinal mucosa were unaffected. Stimulation by exogenous CCK or inhibition of exogenous CCK by devazepide rapidly increased or decreased the cell profileration in pancreatic acinar cells, respectivley, followed by corresponding effects on weight, protein and DNA contents. Devazepide also induced hyperplasia in both liver and bilary tract. The parotid glands were unaffected by both CCK and devazepide, incaring that the growth induced by PBD and the hypotrophy during TPN were not related to changes in plasma CCK. EGF induced after several days increased cell profileration in all exocrine cell types in the pancreas and salivary glands. Thus, both EGF and CCK exerted a mitogenic effect on the pancreas, although effecting different cell types with different time course, whereas EGF but not CCK influenced the parotid glands.