INHIBITION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE OBTAINED FROM GUINEA-PIG KIDNEY BY FUROSEMIDE, NARINGENIN AND SOME OTHER COMPOUNDS

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) can cause excess mineralocorticoid effects and hypokalemia, Several substa nces causing hypokalemia (glycyrrhizic acid in licorice and gossypol) inhibit this enzyme. We tested other compounds for activity to inhibit 11 beta-OHSD in guinea pig kidney cortex microsomes with NADP as cofa ctor and cortisol as substrate. Furosemide was an inhibitor while bume tanide was not, indicating a mechanism for the increased K+ excretion caused by furosemide compared with bumetanide. Naringenin (found in gr apefruit juice), ethacrynic acid, and chenodeoxycholic acid had inhibi tor IC50 values similar to glycyrrhizic acid. We conclude that various compounds can inhibit this enzyme and may play a role in K+ metabolis m and adrenocorticosteroid action.