Binding and antimineralocorticoid activities of spirolactones in toad bladder

Details

Serval ID
serval:BIB_E4DD7BE27139
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Binding and antimineralocorticoid activities of spirolactones in toad bladder
Journal
American Journal of Physiology
Author(s)
Rossier  B. C., Claire  M., Rafestin-Oblin  M. E., Geering  K., Gaggeler  H. P., Corvol  P.
ISSN
0363-6143
Publication state
Published
Issued date
01/1983
Volume
244
Number
1
Pages
C24-31
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
The role of the soluble pool (cytoplasmic or cytosolic) of [3H]-aldosterone binding sites in the toad bladder was assessed by the use of two spirolactones, prorenone and spironolactone as a reference drug. Prorenone fulfills all the criteria for a specific competitive antagonist of aldosterone for its effect on Na+ transport. Compared with spironolactone (Ki approximately equal to 1 microM), prorenone was about eightfold less potent (Ki approximately equal to 8 microM). Competition for [3H]aldosterone binding sites by spironolactone and prorenone revealed an order of potency (spironolactone greater than prorenone) that corresponded to their antagonist activities in the Na+ transport assay. There was a linear correlation between the effects of the two spirolactones on the aldosterone-stimulated Na+ transport and their ability to displace [3H]aldosterone from its binding sites in the soluble pool. Finally [3H]prorenone binding sites were detected in the soluble pool but an insignificant number of antagonist-receptor complexes were found associated with the nuclear pool. Our study indicates that the aldosterone binding sites of the soluble pool are indeed mineralocorticoid receptors, which are probably the first intracellular mediators leading to an increased Na+ reabsorption.
Keywords
Aldosterone/metabolism *Aldosterone Antagonists Animals Binding, Competitive Biological Transport/drug effects Bufo marinus Female Male Receptors, Aldosterone Receptors, Glucocorticoid/*metabolism Receptors, Steroid/*metabolism Sodium/metabolism Spironolactone/*analogs & derivatives/metabolism/*pharmacology Urinary Bladder/*metabolism
Pubmed
Web of science
Create date
24/01/2008 13:00
Last modification date
20/08/2019 16:08
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