Furosemide inhibits 11beta-hydroxysteroid dehydrogenase type 2.

Fuster, Daniel Guido; Escher, Geneviève; Vogt, Bruno; Ackermann, Daniel; Dick, Bernhard; Frey, B M; Frey, F J (1998). Furosemide inhibits 11beta-hydroxysteroid dehydrogenase type 2. Endocrinology, 139(9), pp. 3849-54. Endocrine Society 10.1210/endo.139.9.6175

Full text not available from this repository. (Request a copy)

11Beta-hydroxsteroid dehydrogenase 2 (11beta-OHSD2) protects the nonselective renal mineralocorticoid receptor from the endogenous glucocorticoid cortisol. Thus, drugs inhibiting 11beta-OHSD2 might enhance urinary loss of potassium. As diuretics influence the renal handling of potassium, we analyzed the impact of 13 commonly used diuretics on 11beta-OHSD2. Furosemide was the only inhibitor. Its inhibition constant (Ki) was 30 micromol when extracts from COS-1 cells transfected with human 11beta-OHSD2 were used as an enzyme source. The type of inhibition was competitive. To establish whether furosemide inhibits 11beta-OHSD2 and 11beta-OHSD1 in the renal target tissue, isolated tubular segments from rats were analyzed. Furosemide decreased the oxidative activity of 11beta-OHSD2 in intact distal tubules and 11beta-OHSD1 in proximal convoluted tubules. For the assessment of furosemide on the excretion of corticosterone metabolites in vivo, rats were given furosemide i.p., and the ratio of tetrahydrocorticosterone plus 5alpha-tetrahydrocorticosterone to 11-dehydrotetrahydrocorticosterone was determined in urine. This ratio increased after the administration of furosemide in all animals, indicating inhibition of the oxidative activity of 11beta-OHSD. Thus, furosemide inhibits the 11beta-OHSD2 enzyme in the target tissue and might by that mechanism enhance the mineralocorticoid effect of 11beta-hydroxyglucocorticoids.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

UniBE Contributor:

Fuster, Daniel Guido; Escher, Geneviève; Vogt, Bruno; Ackermann, Daniel and Dick, Bernhard

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0013-7227

Publisher:

Endocrine Society

Language:

English

Submitter:

Daniel Fuster

Date Deposited:

21 Jan 2016 10:30

Last Modified:

21 Jan 2016 10:30

Publisher DOI:

10.1210/endo.139.9.6175

PubMed ID:

9724039

URI:

https://boris.unibe.ch/id/eprint/51130

Actions (login required)

Edit item Edit item
Provide Feedback