Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI

Am J Physiol Cell Physiol. 2004 Apr;286(4):C952-64. doi: 10.1152/ajpcell.00266.2003. Epub 2003 Nov 12.

Abstract

Lithium treatment for 4 wk caused severe polyuria, dramatic downregulation in aquaporin-2 (AQP-2) expression, and marked decrease in AQP-2 immunoreactivity with the appearance of a large number of cells without AQP-2 labeling in the collecting ducts after lithium treatment. Surprisingly, this was not all due to an increase in AQP-2-negative principal cells, because double immunolabeling revealed that the majority of the AQP-2-negative cells displayed [H(+)]ATPase labeling, which identified them as intercalated cells. Moreover, multiple [H(+)]ATPase-labeled cells were adjacent, which was never seen in control rats. Quantitation confirmed a significant decrease in the fraction of collecting duct cells that exhibited detectable AQP-2 labeling compared with control rats: in cortical collecting ducts, 40 +/- 3.4 vs. 62 +/- 1.8% of controls (P < 0.05; n = 4) and in inner medullary collecting ducts, 58 +/- 1.6 vs. 81 +/- 1.3% of controls (P < 0.05; n = 4). In parallel, a significant increase in the fraction of intercalated ([H(+)]ATPase-positive) cells was shown. Urine output, whole kidney AQP-2 expression, cellular organization, and the fractions of principal and intercalated cells in cortex and inner medulla returned to control levels after 4 wk on a lithium-free diet following 4 wk on a lithium-containing diet. In conclusion, lithium treatment not only decreased AQP-2 expression, but dramatically and reversibly reduced the fraction of principal cells and altered the cellular organization in collecting ducts. These effects are likely to be important in lithium-induced nephrogenic diabetes insipidus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Aquaporin 2
  • Aquaporin 4
  • Aquaporin 6
  • Aquaporins / immunology
  • Aquaporins / metabolism
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Diabetes Insipidus, Nephrogenic / chemically induced*
  • Diabetes Insipidus, Nephrogenic / metabolism*
  • Down-Regulation / drug effects
  • Kidney Tubules, Collecting / drug effects*
  • Kidney Tubules, Collecting / metabolism*
  • Kidney Tubules, Collecting / ultrastructure
  • Lithium / pharmacology*
  • Membrane Transport Proteins*
  • Microscopy, Immunoelectron
  • Proton-Translocating ATPases / immunology
  • Proton-Translocating ATPases / metabolism
  • Rats
  • Rats, Wistar
  • Recovery of Function
  • Sulfate Transporters
  • Urine

Substances

  • Antibodies
  • Aqp2 protein, rat
  • Aqp4 protein, rat
  • Aquaporin 2
  • Aquaporin 4
  • Aquaporin 6
  • Aquaporins
  • Carrier Proteins
  • Membrane Transport Proteins
  • SLC26A4 protein, human
  • Sulfate Transporters
  • Lithium
  • Proton-Translocating ATPases