alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.

Détails

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Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_CC4C51D43271
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.
Périodique
Journal of the American Society of Nephrology
Auteur(s)
Christensen B.M., Zuber A.M., Loffing J., Stehle J.C., Deen P.M., Rossier B.C., Hummler E.
ISSN
1533-3450 (Electronic)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
2011
Volume
22
Numéro
2
Pages
253-261
Langue
anglais
Résumé
Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic lithium treatment. In contrast to control mice, KO mice did not markedly increase their water intake. Furthermore, KO mice did not demonstrate the polyuria and reduction in urine osmolality induced by lithium treatment in the control mice. Lithium treatment reduced AQP2 protein levels in the cortex/outer medulla and inner medulla (IM) of control mice but only partially reduced AQP2 levels in the IM of KO mice. Furthermore, lithium induced expression of H(+)-ATPase in the IM of control mice but not KO mice. In conclusion, the absence of functional ENaC in the CD protects mice from lithium-induced NDI. These data support the hypothesis that ENaC-mediated lithium entry into the CD principal cells contributes to the pathogenesis of lithium-induced NDI.
Mots-clé
Absorption, Animals, Aquaporin 2/analysis, Diabetes Insipidus, Nephrogenic/chemically induced, Epithelial Sodium Channel/physiology, Kidney Tubules, Collecting/metabolism, Kidney Tubules, Collecting/pathology, Lithium Chloride/pharmacokinetics, Lithium Chloride/toxicity, Mice, Mice, Knockout, Proton-Translocating ATPases/analysis
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/03/2011 12:36
Dernière modification de la notice
09/05/2019 1:20
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