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This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/F550    most recent 00029.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Kim, Y.-H. Articles by Madsen, K. M. Search for Related Content PubMed PubMed Citation Articles by Kim, Y.-H. Articles by Madsen, K. M.

Increased expression of H⁺-ATPase in inner medullary collecting duct of aquaporin-1-deficient mice

¹Department of Medicine, University of Florida, Gainesville, Florida 32610-0215; ²Department of Anatomy, Catholic University Medical College, Seoul 137-701, Korea; and ³Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521

Submitted 23 January 2003 ; accepted in final form 7 May 2003

Phenotype analysis has demonstrated that aquaporin-1 (AQP1) null mice are polyuric and manifest a urinary concentrating defect because of an inability to create a hypertonic medullary interstitium. We report here that deletion of AQP1 is also associated with a decrease in urinary pH from 6.15 ± (SE) 0.1 to 5.63 ± 0.07. To explore the mechanism of the decrease in urinary pH, we examined the expression of H⁺-ATPase in kidneys of AQP1 null mice. There was strong labeling for H⁺-ATPase in intercalated cells and proximal tubule cells in both AQP1 null and wild-type mice. Strong H⁺-ATPase immunostaining was also present in the apical plasma membrane of inner medullary collecting duct (IMCD) cells in AQP1 null mice, whereas no H⁺-ATPase labeling was observed in IMCD cells in wild-type mice. In addition, there was an increase in the prevalence of type A intercalated cells in the IMCD of AQP1 null mice, suggesting that the deletion of intercalated cells from the IMCD, which normally occurs during postnatal kidney development, was impaired. Western blot analysis of H⁺-ATPase expression in the different regions of the kidney demonstrated a significant increase in H⁺-ATPase protein in the inner medulla of AQP1 null mice compared with wild-type mice. There were no changes in H⁺-ATPase expression in the cortex or outer medulla. These results represent the first demonstration of apical H⁺-ATPase immunoreactivity in IMCD cells in vivo and suggest that the decrease in urinary pH observed in AQP1 null mice is due to upregulation of H⁺-ATPase in the IMCD. The induction of H⁺-ATPase expression in IMCD cells of AQP1 null mice may be related to the chronically low interstitial osmolality in these animals. The challenge will be to identify the molecular signal(s) responsible for the de novo H⁺-ATPase expression.

urine acidification; intercalated cells; immunohistochemistry

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