EFFECT OF L-364,718 (CCK RECEPTOR ANTAGONIST) ON EXOCRINE PANCREATIC-SECRETION OF HYDROCORTISONE-TREATED RATS

Exocrine pancreatic function was studied in control rats and animals subjected to treatment with hydrocortisone (10 mg/kg/day) over 7 days. In both cases, the cholecystokinin (CCK) receptor antagonist L-364,718 (0.1 mg/kg/day) had been administered. The administration of this nonpeptide CCK antagonist significantly reduced the basal pancreatic flow of secretion and enzymes in the control rats but did not cause a decrease in pancreatic weight. From this it may be inferred that factors other than CCK are able to exert the trophic effects of this hormone. Also, the processes of enzyme synthesis and storage, which contribute to maintaining the weight of the organ, continued to occur under conditions of deprivation of the action of endogenous CCK because pan creatic secretion in response to the infusion of CCK was similar in the animals treated and not treated with L-364,718. In contrast, no significant changes were observed either regarding pancreatic weight or basal pancreatic secretion in the animals treated with hydrocortisone and simultaneously with L-364,718, as compared with the rats treated only with hydrocortisone. This points to a predominant effect of glucocorticoids on the action of CCK during the phases of enzyme synthesis and storage, accompanied by a blockade of exocytosis due to hydrocortisone treatment. The secretagogue effect of CCK alone becomes possible with high levels of this hormone of exogeneous origin, whose interaction with its specific receptors is in turn positively modulated by an excess of glucocorticoids.