Influence of Adrenalectomy on Pancreatic Enzyme Secretion

Abstract

Both adrenalectomy and chemically induced diabetes mellitus cause a marked decrease of pancreatic amylase synthesis in rats. Diabetes is further associated with alterations of cholecystokinin (CCK)-stimulated enzyme secretion. Using isolated pancreatic acini prepared from adrenalectomized male rats, we investigated the effects of adrenalectomy on pancreatic enzyme secretion. CCK8-stimulated amylase secretion showed a typical biphasic dose-response curve in acini from both adrenalectomized and sham-operated animals with similar basal secretions, similar sensitivities to various CCK8 concentrations, but a statistically significant elevation of maximal amylase secretion after adrenalectomy. Receptor-binding studies with 125I-BH-CCK8 revealed an increase of binding to the high-affinity part of the CCK receptor in adrenalectomized rats. While carbachol-stimulated secretion showed no changes in maximal secretion rates, it did show a decrease in sensitivity in adrenalectomized animals with a statistically significant shift to the right of the dose-response curves. Competitive inhibition curves with 3H-N-methylscopolamine and carbachol as the competitive receptor agonist showed no differences in receptor binding between controls and adrenalectomized rats. We propose that complex alterations in hormone/neurotransmitter-stimulated pancreatic enzyme secretion are found in glucocorticoid depletion, explainable via a postreceptor defect in carbachol-stimulated secretion. The functional and binding data with regard to CCK are more difficult to explain.