Inhibition of 11β-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 substances 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 cofactor and cortisol as substrate. Furosemide was an inhibitor while bumetanide was not, indicating a mechanism for the increase K+ excretion caused by furosemide compared with bumetanide. Naringenin (found in grapefruit juice), ethacrynic acid, and chenodeoxycholic acid had inhibitor IC50 values similar to glycyrrhizic acid. We conclude that various compounds can inhibit this enzyme and may play a role in K+ metabolism and adrenocorticosteroid action.