We examined the role of physiologic plasma concentrations of cholecystokinin (CCK) in the regulation of rat pancreatic gene expression. Postprandial plasma CCK concentrations, as determined by bioassay, were achieved by intraduodenal perfusion with soybean trypsin inhibitor (SBTI) or intravenous infusion of CCK-8. SBTI administration for 48h resulted in nonparallel regulation of digestive enzyme gene expression, as assessed by slot-blot analysis using cloned cDNA probes for trypsin, chymotrypsin, amylase and ribonuclease. As an indicator for pancretic growth stimulation, ornithine decarboxylase (ODC) gene expression was stimulated appr. 2-fold over the SBTI infusion period. Identical effects were seen with i.v. infusion of CCK-8. The CCK receptor antagonist L-364, 718 blocked the effects on pancreatic gene expression of both CCK infusion and SBTI administration. These data therefore indicate that postprandial plasma CCK concentrations regulate pancreatic digestive enzyme and ODC gene expression at a pretranslational level.
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