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Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney
Cited 18 time in
Web of Science
Cited 19 time in Scopus
- Authors
- Issue Date
- 2007
- Publisher
- American Physiological Society
- Citation
- Am J Physiol Renal Physiol 292:F1701-F1709, 2007
- Keywords
- Animals ; Blotting, Western ; Chloride-Bicarbonate Antiporters/metabolism ; Diuretics/*pharmacology ; Electrophoresis, Polyacrylamide Gel ; Furosemide/*pharmacology ; Hydrochlorothiazide/*pharmacology ; Immunohistochemistry ; Kidney/drug effects/*enzymology/pathology ; Male ; Proton-Translocating ATPases/*biosynthesis/immunology ; RNA/biosynthesis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium/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
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