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

Cited 17 time in Web of Science Cited 18 time in Scopus
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
2007
Publisher
American Physiological Society
Citation
Am J Physiol Renal Physiol 292:F1701-F1709, 2007
Keywords
AnimalsBlotting, WesternChloride-Bicarbonate Antiporters/metabolismDiuretics/*pharmacologyElectrophoresis, Polyacrylamide GelFurosemide/*pharmacologyHydrochlorothiazide/*pharmacologyImmunohistochemistryKidney/drug effects/*enzymology/pathologyMaleProton-Translocating ATPases/*biosynthesis/immunologyRNA/biosynthesisRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionSodium/metabolism
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 approximately 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.
ISSN
0363-6127 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17311909

https://hdl.handle.net/10371/23408
DOI
https://doi.org/10.1152/ajprenal.00270.2006
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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