alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.

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Christensen BM, Zuber AM, Loffing J, Stehle JC, Deen PM, Rossier BC, Hummler E

alphaENaC-mediated lithium absorption promotes nephrogenic diabetes insipidus.

J Am Soc Nephrol. 2011 Feb;22(2):253-61. doi: 10.1681/ASN.2010070734. Epub 2010 Nov 4.

PubMed ID
21051735 [ View in PubMed
]
Abstract

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 alphaENaC 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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
Lithium carbonateAmiloride-sensitive sodium channel subunit alphaProteinHumans
Unknown
Not AvailableDetails
Lithium carbonateAmiloride-sensitive sodium channel subunit betaProteinHumans
Unknown
Not AvailableDetails
Lithium carbonateAmiloride-sensitive sodium channel subunit gammaProteinHumans
Unknown
Not AvailableDetails