Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts
Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts
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DOI：
10.1038/hr.2009.19
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发表时间：
2009-05
影响因子：
5.4
通讯作者：
T. Mouri;Takeaki Inoue;H. Nonoguchi;Y. Nakayama;Hiroki Miyazaki;T. Matsuzaki;H. Saito;T. Nakanishi;Y. Kohda;K. Tomita
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文献类型：
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作者：
T. Mouri;Takeaki Inoue;H. Nonoguchi;Y. Nakayama;Hiroki Miyazaki;T. Matsuzaki;H. Saito;T. Nakanishi;Y. Kohda;K. Tomita
肾脏水通道蛋白2（AQP 2）的表达在尿液浓缩中起关键作用。然而，目前尚不清楚代谢性酸中毒是否通过肾脏和尿液中的AQP 2表达影响尿液浓缩能力。我们检测了对照组和酸中毒组大鼠尿液排泄和肾脏AQP 2的表达，采用RT-竞争PCR，免疫印迹和免疫细胞化学。代谢性酸中毒大鼠集合管中AQP 2 mRNA和蛋白表达增加，尿中AQP 2排泄量减少92%。对照组大鼠尿渗透压为1670±198 mOsm/kg H2 O，免疫细胞化学显示集合管主细胞顶端质膜存在AQP 2。尿渗透压（1397±243 mOsm/kg H2O）低于对照组，免疫细胞化学显示AQP 2弥散分布于主细胞胞浆。差速离心偶联免疫印迹显示，代谢性酸中毒的质膜富集组分中的AQP 2与胞内囊泡富集组分中的AQP 2的比率显著降低。总之，代谢性酸中毒可显著降低AQP 2易位，即使集合管表达增加。结论：慢性肾功能衰竭患者的利尿作用可能与集合管AQP 2转位紊乱有关。
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.