Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney
- Authors
- Na, Ki Young; Kim, Gheun-Ho; Joo, Kwon Wook; Lee, Jay Wook; Jang, Hye Ryoun; Oh, Yun Kyu; Jeon, Un Sil; Chae, Seoung-Wan; Knepper, Mark A.; Han, Jin Suk
- Issue Date
- Jun-2007
- Publisher
- AMER PHYSIOLOGICAL SOC
- Keywords
- distal acidification; amiloride; polyclonal anti-H+-ATPase B1 subunit antibody; pendrin; intercalated cells
- Citation
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.292, no.6, pp.F1701 - F1709
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
- Volume
- 292
- Number
- 6
- Start Page
- F1701
- End Page
- F1709
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172294
- DOI
- 10.1152/ajprenal.00270.2006
- ISSN
- 1931-857X
- Abstract
- 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 similar to 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.
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