EFFECTS OF CARBENOXOLONE ADMINISTERED ACUTELY TO ADRENALECTOMIZED RATS (INVIVO) ON RENAL AND HEPATIC HANDLING OF CORTICOSTERONE BY 11-BETA-HYDROXYSTEROID DEHYDROGENASE

The in vivo effect(s) of carbenoxolone (CS) on renal 11beta-hydroxysteroid dehydrogenase (11beta-OHSD), hepatic 11beta-OHSD, and 5beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11beta-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 muM and 50 muM corticosterone, as was 5beta-reductase (P < 0.05) using 4 muM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11beta-OHSD and 5beta-reductase with no inhibition of renal 11beta-OHSD. We conclude that further experiments are necessary to determine whether CS truly inhibits renal 11beta-OHSD in vivo, and whether hepatic handling of corticosterone also plays an important role in regulating its MC-like activity.