Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient
Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient
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DOI：
10.1152/ajprenal.00405.2002
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发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Pritchard, JB
中科院分区：
文献类型：
--
作者：
Sweet, DH;Chan, LMS;Pritchard, JB
肾近端小管细胞对有机阴离子的基底侧摄取通过Na+二羧酸盐共转运和有机阴离子/二羧酸盐交换与Na+梯度间接偶联。有机阴离子转运蛋白（OAT）家族的一个成员Oat 1在近端小管中表达，是一种有机阴离子/二羧酸盐交换剂。然而，第二种有机阴离子载体Oat 3也在肾近端小管中高度表达，但其机制尚不清楚。因此，我们评估了燕麦3功能非洲爪蟾卵母细胞和大鼠肾皮质切片。丙磺舒敏感的摄取对氨基马尿酸盐（PAH，燕麦1和燕麦3基板）和雌酮硫酸盐（ES，燕麦3基板）在大鼠Oat 3表达卵母细胞显着trans-stimulated预加载的卵母细胞与二羧酸戊二酸（GA）。GA刺激ES运输共表达兔Na+二羧酸转运蛋白1和大鼠Oat 3的卵母细胞显着抑制时，预加载培养基中含有Li+或琥珀酸甲酯（MS）或当Na+不存在。所有这些治疗抑制Na+-二羧酸协同转运蛋白，但不大鼠燕麦3。Li+，MS和Na+去除没有效果时，在ES吸收步骤，而不是在GA预加载步骤。大鼠肾皮质切片中的浓缩ES摄取也被证明是丙磺舒和Na+敏感的。GA刺激ES的积累，丙磺舒、Li+、MS、牛磺胆酸盐和去除N+可完全阻断这种刺激。因此，Oat 3作为有机阴离子/二羧酸盐交换剂，将有机阴离子吸收间接耦合到Na+梯度。
Basolateral uptake of organic anions in renal proximal tubule cells is indirectly coupled to the Na+ gradient through Na+ dicarboxylate cotransport and organic anion/dicarboxylate exchange. One member of the organic anion transporter (OAT) family, Oat1, is expressed in the proximal tubule and is an organic anion/dicarboxylate exchanger. However, a second organic anion carrier, Oat3, is also highly expressed in the renal proximal tubule, but its mechanism is unclear. Thus we have assessed Oat3 function in Xenopus laevis oocytes and rat renal cortical slices. Probenecid-sensitive uptake of p-aminohippurate (PAH, an Oat1 and Oat3 substrate) and estrone sulfate (ES, an Oat3 substrate) in rat Oat3-expressing oocytes was significantly trans-stimulated by preloading the oocytes with the dicarboxylate glutarate (GA). GA stimulation of ES transport by oocytes coexpressing rabbit Na+ dicarboxylate cotransporter 1 and rat Oat3 was significantly inhibited when the preloading medium contained Li+ or methylsuccinate (MS) or when Na+ was absent. All these treatments inhibit the Na+-dicarboxylate cotransporter, but not rat Oat3. Li+, MS, and Na+ removal had no effect when applied during the ES uptake step, rather than during the GA preloading step. Concentrative ES uptake in rat renal cortical slices was also demonstrated to be probenecid and Na+ sensitive. Accumulation of ES was stimulated by GA, and this stimulation was completely blocked by probenecid, Li+, MS, taurocholate, and removal of N+. Thus Oat3 functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the Na+ gradient.