Effects of cholecystokinin on the pituitary-adrenal axis of rats with intact or regenerating adrenal glands

Cholecystokinin (CCK) is a regulatory peptide, widely distributed in the bo dy tissues and organs, which acts through two subtypes of receptors (R), na med CCKA-R and CCKB-R. CCK and its receptors are contained in both the cent ral and peripheral branches of the hypothalamo-pituitary-adrenal (HPA) axis , and we have investigated the effects of the administration of CCK-8 and i ts receptor antagonists (RA) (three subcutaneous injections of 20 nmol/kg, 24, 16 and 4 h before the sacrifice) on the plasma concentrations of ACTH, aldosterone and corticosterone in rats with intact or regenerating adrenal glands deprived of medullary chromaffin cells. CCK-8 increased ACTH and cor ticosterone (but not aldosterone) plasma levels in intact rats, and the eff ect was annulled by the simultaneous injection of the CCKA-RA, but not CCKB -RA antagonist. The CCK-RAs alone did not alter plasma hormonal levels. As expected, rats with regenerating adrenals displayed high blood levels of AC TH and low levels of aldosterone and corticosterone. CCK-8 did not affect A CTH, aldosterone, and corticosterone plasma concentrations in operated rats . CCKA-RA, but not CCKB-RA raised corticosterone (but not aldosterone) bloo d level, and the effect was abolished by the simultaneous administration of CCK-8. These findings allow us to conclude that: (i) CCK, through the acti vation of the CCKA-R, stimulates HPA axis in rats with intact adrenals, but the physiological relevance of this effect remains to be demonstrated; and (ii) endogenous CCK exerts a CCKA-R-mediated tonic inhibition of corticost erone secretion during adrenal regeneration.