Document Detail


Aldosterone and mineralocorticoid receptors: orphan questions.
MedLine Citation:
PMID:  10760067     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Classically, mineralocorticoid receptors (MR) are activated by aldosterone to promote unidirectional transepithelial sodium transport. Activation of MR in nonepithelial tissues has been shown to elevate blood pressure (central nervous system; CNS) and to cause hypertrophy and fibrosis (heart). For both epithelial and nonepithelial tissues, there remain a variety of questions regarding MR which are not only unanswered but also essentially not addressed. Seven such questions include: (1) how the physiologic glucocorticoids (cortisol and corticosterone) can mimic aldosterone action in epithelial MR, but act as antagonists in the heart and AV3V region; (2) how salt facilitates the nonepithelial, pathophysiologic effects of aldosterone; (3) how aldosterone activates unprotected AV3V MR in the face of orders of magnitude higher circulating glucocorticoid concentrations; (4) how unprotected nonepithelial MR act as "always occupied" receptors in guinea pigs and other species; (5) how, when 11beta hydroxysteroid dehydrogenase type 2 is active, epithelial MR occupied by physiologic glucocorticoids appear transcriptionally inactive; (6) how aldosterone activates epithelial MR in the face of approximately 103-fold higher glucocorticoid levels, plasma binding and 11beta hydroxysteroid dehydrogenase type 2 activity notwithstanding; and (7) how aldosterone produces changes in urinary [K+] before [Na+].
Authors:
J W Funder
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Kidney international     Volume:  57     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-09     Completed Date:  2000-05-09     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1358-63     Citation Subset:  IM    
Affiliation:
Baker Medical Research Institute, Melbourne, Australia. sue.smith@baker.edu.au
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenases
Aldosterone / physiology
Animals
Corticosterone / physiology
Glucocorticoids / metabolism
Hydrocortisone / physiology
Hydroxysteroid Dehydrogenases / metabolism
Receptors, Aldosterone / physiology*
Receptors, Mineralocorticoid / physiology*
Sodium Chloride / pharmacology
Chemical
Reg. No./Substance:
0/Glucocorticoids; 0/Receptors, Aldosterone; 0/Receptors, Mineralocorticoid; 50-22-6/Corticosterone; 50-23-7/Hydrocortisone; 52-39-1/Aldosterone; 7647-14-5/Sodium Chloride; EC 1.1.-/Hydroxysteroid Dehydrogenases; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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