S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney
- 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
- American Physiological Society
- Am J Physiol Renal Physiol 292:F1701-F1709, 2007
- 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
- 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.
- 0363-6127 (Print)
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