Organic anion transporter OAT1 is involved in renal handling of citrulline
Organic anion transporter OAT1 is involved in renal handling of citrulline
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DOI：
10.1152/ajprenal.90662.2008
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发表时间：
2009-07-01
影响因子：
4.2
通讯作者：
Tamai, Ikumi
中科院分区：
文献类型：
--
作者：
Nakakariya, Masanori;Shima, Yoichiro;Tamai, Ikumi
王晓明，王晓明，王晓明，等。有机阴离子转运蛋白OAT1在瓜氨酸肾处理中的作用。[J] .中国生物医学工程学报，2009,31(4):571 - 579。首次发表于2009年4月29日；doi: 10.1152 / ajprenal.90662.2008。由于肾衰竭时瓜氨酸血浆浓度升高，瓜氨酸可能是肾功能不全的生物标志物，尽管其在肾脏中的调节机制尚不清楚。在大鼠肾片中，瓜氨酸的摄取明显依赖于Na+， K-m 556 μ M可饱和，阴离子（PAH）和阳离子（TEA）化合物显著抑制瓜氨酸的摄取，而probenecid在1 mM时不抑制瓜氨酸的摄取。与戊二酸预孵育的肾片增加了瓜氨酸的摄取，而在无Na+缓冲液中预孵育后没有观察到这种增加。这一结果表明，钠依赖性二羧酸共转运体参与了大鼠肾片对瓜氨酸的摄取。在转运蛋白过表达细胞的研究中，人类有机阴离子转运蛋白1 （OAT1）和大鼠OAT1表现出瓜氨酸转运活性，Km值分别为238和373 μ M，而其他燕麦和有机阳离子转运蛋白（OCTs）不转运瓜氨酸。基于相对活性因子法，大鼠Oat1对大鼠肾片瓜氨酸整体摄取的贡献接近70%。此外，通过大鼠Oat1摄取瓜氨酸、多环芳烃和probenecid之间的相互作用表明，Oat1上存在多个功能位点，瓜氨酸位点可能与多环芳烃和probenecid位点不同。因此，OAT1/ OAT1似乎是肾基底外侧摄取瓜氨酸的主要贡献者之一，这些转运蛋白的活性受损可能在很大程度上导致肾衰竭时血浆瓜氨酸的增加。因此，瓜氨酸和肌酐可用于诊断肾功能。
Nakakariya M, Shima Y, Shirasaka Y, Mitsuoka K, Nakanishi T, Tamai I. Organic anion transporter OAT1 is involved in renal handling of citrulline. Am J Physiol Renal Physiol 297: F71-F79, 2009. First published April 29, 2009; doi:10.1152/ajprenal.90662.2008.-Because citrulline plasma concentration is elevated in kidney failure, citrulline could be a biomarker of renal insufficiency, although the mechanism regulating its disposition in the kidney has not been clarified. In rat kidney slices, citrulline uptake was apparently Na+ dependent, saturable with K-m 556 mu M, and significantly inhibited by anionic (PAH) and cationic ( TEA) compounds, but not by probenecid at 1 mM. Preincubation of kidney slices with glutarate increased citrulline uptake, while such an increase was not observed after preincubation of the slices in Na+-free buffer. This result suggested that a sodium-dependent dicarboxylate cotransporter is involved in citrulline uptake by rat kidney slices. In studies using transporter-overexpressing cells, human organic anion transporter 1 ( OAT1) and rat Oat1 exhibited citrulline transport activity with Km values of 238 and 373 mu M, respectively, while other OATs and organic cation transporters (OCTs) did not transport citrulline. Based on the relative activity factor method, the contribution of rat Oat1 to the overall uptake of citrulline in rat kidney slices was similar to 70%. Moreover, the interaction among citrulline, PAH, and probenecid uptakes via rat Oat1 suggested that there are multiple functional sites on Oat1 and that the citrulline site may be distinct from the PAH and probenecid site. Thus OAT1/Oat1 appears to be one of the major contributors to renal basolateral uptake of citrulline, and impaired activities of these transporters may contribute substantially to the increase in plasma citrulline in renal failure. Accordingly, citrulline may be useful for diagnosis of kidney function as is creatinine.