Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosterone-stimulated sodium transport in a novel renal cell line

Détails

ID Serval
serval:BIB_893A008B5496
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosterone-stimulated sodium transport in a novel renal cell line
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Gaeggeler  H. P., Gonzalez-Rodriguez  E., Jaeger  N. F., Loffing-Cueni  D., Norregaard  R., Loffing  J., Horisberger  J. D., Rossier  B. C.
ISSN
1046-6673 (Print)
Statut éditorial
Publié
Date de publication
04/2005
Volume
16
Numéro
4
Pages
878-91
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
Aldosterone controls sodium balance by regulating an epithelial sodium channel (ENaC)-mediated sodium transport along the aldosterone-sensitive distal nephron, which expresses both mineralocorticoid (MR) and glucocorticoid receptors (GR). Mineralocorticoid specificity is ensured by 11beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol or corticosterone into inactive metabolites that are unable to bind MR and/or GR. The fractional occupancy of MR and GR by aldosterone mediating the sodium transport response in the aldosterone-sensitive distal nephron cannot be studied in vivo. For answering this question, a novel mouse cortical collecting duct cell line (mCCD(cl1)), which expresses significant levels of MR and GR and a robust aldosterone sodium transport response, was used. Aldosterone elicited a biphasic response: Low doses (K(1/2) = approximately 0.5 nM) induced a transient and early increase of sodium transport (peaking at 3 h), whereas high doses (K(1/2) = approximately 90 nM) entailed an approximately threefold larger, long-lasting response. At 3 h, the corticosterone dose-response curve was shifted to the right compared with that of aldosterone by more than two log concentrations, an effect that was fully reverted in the presence of the 11beta-hydroxysteroid dehydrogenase type 2 inhibitor carbenoxolone. Low doses of dexamethasone (0.1 to 1 nM) failed to induce an early response, but high doses elicited a long-lasting response (K(1/2) = approximately 8 nM), similar to that observed for high aldosterone concentrations. Equilibrium binding assays showed that both aldosterone and corticosterone bind to a high-affinity, low-capacity site, whereas dexamethasone binds to one site. Within the physiologic range of aldosterone concentrations, sodium transport is predicted to be controlled by MR occupancy during circadian cycles and by MR and GR occupancy during salt restriction or acute stress.
Mots-clé
11-beta-Hydroxysteroid Dehydrogenases/metabolism Aldosterone/administration & dosage/*pharmacology Animals Binding, Competitive Biological Transport/drug effects Cell Line, Transformed Corticosterone/administration & dosage/pharmacology Dexamethasone/administration & dosage/pharmacology Dose-Response Relationship, Drug Glucocorticoids/administration & dosage/pharmacology Kidney Tubules, Collecting/cytology/*metabolism Mice Receptors, Glucocorticoid/agonists/*metabolism Receptors, Mineralocorticoid/agonists/*metabolism Sodium/*metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:38
Dernière modification de la notice
20/08/2019 14:48
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