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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/F1701    most recent 00270.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Na, K. Y. Articles by Han, J. S. Search for Related Content PubMed PubMed Citation Articles by Na, K. Y. Articles by Han, J. S.

Chronic furosemide or hydrochlorothiazide administration increases H⁺-ATPase B1 subunit abundance in rat kidney

¹Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute of Seoul National University Hospital, ²Department of Internal Medicine, Hanyang University College of Medicine, and ³Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; and ⁴Laboratory of Kidney and Electrolyte Metabolism, National Institutes of Health, Bethesda, Maryland

Submitted 17 July 2006 ; accepted in final form 13 February 2007

Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H⁺-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H⁺-ATPase and whether electrogenic Na⁺ reabsorption is involved in this process. A 7-day infusion of furosemide or hydrochlorothiazide (HCTZ) lowered urine pH significantly. However, this effect of furosemide-induced distal acidification was not changed with amiloride-blocking electrogenic Na⁺ reabsorption. On immunoblotting, a polyclonal antibody against the H⁺-ATPase B1 subunit recognized a specific 56-kDa band in membrane fractions from the kidney. The protein abundance of H⁺-ATPase was significantly increased by furosemide and HCTZ infusion in both the cortex and outer medulla. Furosemide plus amiloride administration also increased the H⁺-ATPase protein abundance significantly. However, no definite subcellular redistribution of H⁺-ATPase was observed by furosemide ± amiloride infusion with immunohistochemistry. Chronic furosemide ± amiloride administration induced a translocation of pendrin to the apical membrane, while total protein abundance was not increased. The mRNA expression of H⁺-ATPase was not altered by furosemide ± amiloride infusion. We conclude that chronic administration of diuretics enhances distal acidification by increasing the abundance of H⁺-ATPase irrespective of electrogenic Na⁺ reabsorption. This upregulation of H⁺-ATPase in the intercalated cells may be the result of tubular hypertrophy by diuretics.

distal acidification; amiloride; polyclonal anti-H⁺-ATPase B1 subunit antibody; pendrin; intercalated cells