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 s ubjected 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 non peptide CCK antagonist significantly reduced the basal pancreatic flow of secretion and enzymes in the control rats but did not cause a decr ease in pancreatic weight. From this it may be inferred that factors o ther than CCK are able to exert the trophic effects of this hormone. A lso, the processes of enzyme synthesis and storage, which contribute t o maintaining the weight of the organ, continued to occur under condit ions of deprivation of the action of endogenous CCK because pan creati c secretion in response to the infusion of CCK was similar in the anim als treated and not treated with L-364,718. In contrast, no significan t changes were observed either regarding pancreatic weight or basal pa ncreatic secretion in the animals treated with hydrocortisone and simu ltaneously with L-364,718, as compared with the rats treated only with hydrocortisone. This points to a predominant effect of glucocorticoid s on the action of CCK during the phases of enzyme synthesis and stora ge, accompanied by a blockade of exocytosis due to hydrocortisone trea tment. The secretagogue effect of CCK alone becomes possible with high levels of this hormone of exogeneous origin, whose interaction with i ts specific receptors is in turn positively modulated by an excess of glucocorticoids.