αENaC mediated lithium absorption promotes nephrogenic diabetes insipidus
- Mønster Christensen, Birgitte Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland - Water and Salt Research Center, Department of Anatomy, Aarhus University, Denmark
- Mercier Zuber, Annie Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland
- Loffing, Johannes Department of Medicine-Anatomy, University of Fribourg, Switzerland
- Stehle, Jean-Christophe Departments of Pathology, University of Lausanne, Switzerland
- Deen, Peter M.T. Department of Physiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
- Rossier, Bernard C. Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland
- Hummler, Edith Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland
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04.11.2010
Published in:
- Journal of the American Society of Nephrology. - 2011, vol. 22, no. 2, p. 253-261
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 21112
- DOI 10.1681/ASN.2010070734
- Persistent URL
- https://folia.unifr.ch/unifr/documents/301880
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