IN-VIVO AND IN-VITRO EFFECTS OF CARBENOXOLONE ON GLUCOCORTICOID RECEPTOR-BINDING AND GLUCOCORTICOID ACTIVITY

Carbenoxolone potentiates the mineralocorticoid activity of endogenous glucocorticoid hormones by inhibiting the enzyme 11 beta-hydroxystero id dehydrogenase, which converts cortisol and corticosterone to inacti ve 11-oxo-derivatives. We addressed the question of whether glucocorti coid activity is also affected by carbenoxolone. Using a mt model invo lving low dose corticosterone treatment we Sound that carbenoxolone ne ither potentiated nor inhibited the modest increases in blood pressure or reductions in weight gain caused by steroid treatment. Other indic es of glucocorticoid activity including white blood cell number, thymu s weight, and down regulation of the glucocorticoid receptor were unaf fected. In vitro studies with liver and kidney cytosol preparations in dicated that carbenoxolone did compete for H-3-dexamethasone binding s ites. Carbenoxolone was 5-10 times more effective than glycyrrhetinic acid, 20-30 thousand times less effective than dexamethasone, and is, therefore, approximately 1000 times less effective than corticosterone . Analysis of dexamethasone-binding curves indicated a single class of receptor. We conclude that carbenoxolone at the dose rested does not have intrinsic glucocorticoid activity in vivo, nor does it modulate t he activities of corticosterone. Carbenoxolone binds weakly to the glu cocorticoid receptor. It is not clear whether this weak affinity accou nts for some or any of the direct in vitro effects of high concentrati ons of carbenoxolone that others have described. (C) 1997 by Elsevier Science Inc.