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 body tissues and organs, which acts through two subtypes of receptors (R), named CCK(A)-R and CCK(B)-R. CCK and its receptors are contained in both the central and peripheral branches of the hypothalamo-pituitary-adrenal (HPA) axis, and we have investigated the effects of the administration of CCK-8 and its 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 corticosterone (but not aldosterone) plasma levels in intact rats, and the effect was annulled by the simultaneous injection of the CCK(A)-RA, but not CCK(B)-RA antagonist. The CCK-RAs alone did not alter plasma hormonal levels. As expected, rats with regenerating adrenals displayed high blood levels of ACTH and low levels of aldosterone and corticosterone. CCK-8 did not affect ACTH, aldosterone, and corticosterone plasma concentrations in operated rats. CCK(A)-RA, but not CCK(B)-RA raised corticosterone (but not aldosterone) blood level, and the effect was abolished by the simultaneous administration of CCK-8. These findings allow us to conclude that: (i) CCK, through the activation of the CCK(A)-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 CCK(A)-R-mediated tonic inhibition of corticosterone secretion during adrenal regeneration.