Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts.
Renal aquaporin-2 (AQP2) expression plays a key role in urine concentration. However, it is not known whether metabolic acidosis affects urine-concentrating ability through AQP2 expression in the kidney and urine. We examined urinary excretion and renal expression of AQP2 in control and acidosis rats, using RT-competitive PCR, immunoblot and immunocytochemistry. Urinary excretion of AQP2 is decreased by 92% even with the increase in AQP2 mRNA and protein expressions in the collecting ducts by metabolic acidosis in rats. Urine osmolality in control rats was 1670+/-198 mOsm per kg H(2)O, and immunocytochemistry revealed the presence of AQP2 in the apical plasma membrane of the principal cells in the collecting ducts. Urine osmolality in acidosis rats was lower than that in control (1397+/-243 mOsm per kg H(2)O), and immunocytochemistry showed the diffuse presence of AQP2 in the cytoplasm of the principal cells. Differential centrifugation-coupled immunoblot showed a significant decrease in the ratio of AQP2 in plasma membrane-enriched fraction to that in intracellular vesicle-enriched fraction by metabolic acidosis. In summary, AQP2 translocation is largely decreased by metabolic acidosis even with increased expression in the collecting ducts. A disorder of AQP2 translocation in the collecting ducts with acidosis may be responsible for the diuresis in patients with chronic renal failure.
Mouri
Tomohiko
T
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Inoue
Takeaki
T
Nonoguchi
Hiroshi
H
Nakayama
Yushi
Y
Miyazaki
Hiroki
H
Matsuzaki
Takanobu
T
Saito
Hideyuki
H
Nakanishi
Takeshi
T
Kohda
Yukimasa
Y
Tomita
Kimio
K
D000141:Acidosis, Renal Tubular / Q000378:metabolism* / Q000652:urine; D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D009995:Osmosis; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051399:Aquaporin 2; D012333:RNA, Messenger