Altered expression of renal AQPs and Na+ transporters in rats with Lithium-induced NDI

Tae Hwan Kwon, Ulla H. Laursen, David Marples, Arvid B. Maunsbach, Mark A. Knepper, Jørgen Frøkiær, Søren Nielsen

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

Lithium (Li) treatment is often associated with nephrogenic diabetes insipidus (NDI). The changes in whole kidney expression of aquaporin-1 (AQP1), -2, and -3 as well as Na-K-ATPase, type 3 Na/H exchanger (NHE3), type 2 Na-Pi cotransporter (NaPi-2), type 1 bumetanide-sensitive Na-K2Cl cotransporter (BSC-1), and thiazide-sensitive Na-Cl cotransporter (TSC) were examined in rats treated with Li orally for 4 wk: protocol 1, high doses of Li (high Na+ intake), and protocol 2, low doses of Li (identical food and normal Na+ intake in Li-treated and control rats). Both protocols resulted in severe polyuria. Semiquantitative immunoblotting revealed that whole kidney abundance of AQP2 was dramatically reduced to 6% (protocol 1) and 27% (protocol 2) of control levels. In contrast, the abundance of AQP1 was not decreased. Immunoelectron microscopy confirmed the dramatic downregulation of AQP2 and AQP3, whereas AQP4 labeling was not reduced. Li-treated rats had a marked increase in urinary Na+ excretion in both protocols. However, the expression of several major Na+ transporters in the proximal tubule, loop of Henle, and distal convoluted tubule was unchanged in protocol 2, whereas in protocol 1 significantly increased NHE3 and BSC-1 expression or reduced NaPi-2 expression was associated with chronic Li treatment. In conclusion, severe downregulation of AQP2 and AQP3 appears to be important for the development of Li-induced polyuria. In contrast, the increased or unchanged expression of NHE3, BSC-1, Na-K-ATPase, and TSC indicates that these Na+ transporters do not participate in the development of Li-induced polyuria.

Original languageEnglish
Pages (from-to)F552-F564
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number3 48-3
DOIs
StatePublished - 2000

Keywords

  • Aquaporin
  • Nephrogenic diabetes insipidus
  • Sodium transport
  • Urinary concentration mechanism
  • Water transport

Fingerprint

Dive into the research topics of 'Altered expression of renal AQPs and Na+ transporters in rats with Lithium-induced NDI'. Together they form a unique fingerprint.

Cite this