DIFFERENTIAL INHIBITION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE BY CARBENOXOLONE IN RAT-BRAIN REGIONS AND PERIPHERAL-TISSUES

Carbenoxolone (CX), the succinyl ester of glycyrrhetinic acid, causes hypokalemia and hypernatremia. Its pharmacological effects are believe d to be due to its inhibition of 11beta-hydroxysteroid dehydrogenase ( 11-HSD). There was a marked inhibition of this enzyme in the liver, ki dney, pituitary, hippocampus, hypothalamus and amygdala 1 h after intr aperitoneal administration of CX (100 mg kg-1) to intact male rats. In tracerebral injection of CX (1.5 mg kg-1) into the 3rd ventricle inhib ited the oxidation of corticosterone to 11-dehydrocorticosterone by 11 -HSD in the pituitary and hippocampus and produced marked behavioral h yperactivity but had no effect in the liver or kidney. Lower amounts o f CX (10-50 mug/rat) given intracerebroventricularly (i.c.v) were with out significant effect on 11-HSD in the pituitary or amygdala 1 h afte r infusion but inhibited this enzyme differentially in the hippocampus and hypothalamus. Inhibition of 11-HSD activity in the hippocampus an d hypothalamus was observed up to 6 h after i.c.v. administration of C X (50 mug/rat) together with some decrease in activity of this enzyme in the pituitary at 3 h. The findings that low doses of CX given i.c.v . can alter the activity of 11-HSD in specific brain regions without a ffecting its activity in peripheral tissues, and only marginally in th e pituitary, provides a method to study the central role of this enzym e independently of systemic effects.