Furosemide inhibits 11beta-hydroxysteroid dehydrogenase type 2

Details

Serval ID
serval:BIB_7194DF05C466
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Furosemide inhibits 11beta-hydroxysteroid dehydrogenase type 2
Journal
Endocrinology
Author(s)
Fuster  D., Escher  G., Vogt  B., Ackermann  D., Dick  B., Frey  B. M., Frey  F. J.
ISSN
0013-7227 (Print)
Publication state
Published
Issued date
09/1998
Volume
139
Number
9
Pages
3849-54
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Abstract
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.
Keywords
11-beta-Hydroxysteroid Dehydrogenases Animals COS Cells Diuretics/*pharmacology Dose-Response Relationship, Drug Enzyme Inhibitors/*pharmacology Furosemide/*pharmacology Humans Hydroxysteroid Dehydrogenases/*antagonists & inhibitors Kidney Tubules/drug effects/enzymology Male Rats Rats, Wistar Tetrahydrocortisone/urine
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 13:03
Last modification date
20/08/2019 14:30
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