title: Differential inhibition of 11 beta-hydroxysteroid dehydrogenase by carbenoxolone in rat brain regions and peripheral tissues.
abstract: Carbenoxolone (CX), the succinyl ester of glycyrrhetinic acid, causes hypokalemia and hypernatremia. Its pharmacological effects are believed to be due to its inhibition of 11 beta-hydroxysteroid dehydrogenase (11-HSD). There was a marked inhibition of this enzyme in the liver, kidney, pituitary, hippocampus, hypothalamus and amygdala 1 h after intraperitoneal administration of CX (100 mg kg-1) to intact male rats. Intracerebral injection of CX (1.5 mg kg-1) into the 3rd ventricle inhibited the oxidation of corticosterone to 11-dehydrocorticosterone by 11-HSD in the pituitary and hippocampus and produced marked behavioral hyperactivity but had no effect in the liver or kidney. Lower amounts of CX (10-50 micrograms/rat) given intracerebroventricularly (i.c.v) were without significant effect on 11-HSD in the pituitary or amygdala 1 h after infusion but inhibited this enzyme differentially in the hippocampus and hypothalamus. Inhibition of 11-HSD activity in the hippocampus and hypothalamus was observed up to 6 h after i.c.v. administration of CX (50 micrograms/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 affecting its activity in peripheral tissues, and only marginally in the pituitary, provides a method to study the central role of this enzyme independently of systemic effects.
authors.affiliation: Rockefeller University, Laboratory of Neuroendocrinology, New York, NY, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Jellinck
authors.forename: C
authors.initials: C
authors.lastname: Monder
authors.forename: B S
authors.initials: BS
authors.lastname: McEwen
authors.forename: R R
authors.initials: RR
authors.lastname: Sakai
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002229:Carbenoxolone / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone