Role of mouse organic anion transporter 3 (mOat3) as a basolateral prostaglandin E2 transport pathway
Role of mouse organic anion transporter 3 (mOat3) as a basolateral prostaglandin E2 transport pathway
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DOI：
10.1254/jphs.fp0060816
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Endou, Hitoshi
中科院分区：
文献类型：
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作者：
Nilwarangkoon, Sirinun;Anzai, Naohiko;Endou, Hitoshi
肾脏有机阴离子转运蛋白在肾脏处理许多内源性和外源性阴离子物质中发挥着重要作用。在本研究中，我们研究了前列腺素 E-2 (PGE(2)) 转运特性和小鼠有机阴离子转运蛋白 3 (mOat3) 的肾内定位。当在非洲爪蟾卵母细胞中表达时，mOat3 介导 PGE(2) 的时间和浓度依赖性转运（K-m：1.48 μM）。 mOat3 介导的 PGE(2) 转运受到注射到卵母细胞中的细胞内戊二酸的反式刺激。 PGE(2) 通过 mOat3 的流出也受到细胞外戊二酸的反式刺激。因此，mOat3 被证明可以介导 PGE(2) 的双向运输，部分与二羧酸酯交换机制耦合。免疫组织化学研究表明，mOat3 蛋白定位于肾近端和远端肾小管的基底外侧膜。此外，观察到 mOat3 的弥漫性表达，包括在致密斑 (MD) 细胞的基底外侧膜中的表达。这些结果表明mOat3作为包括MD细胞在内的远端肾单位中PGE(2)的基底外侧转运途径发挥着重要作用，这可能构成肾素释放和肾小球反馈机制调节不可或缺的步骤之一。
Renal organic anion transporters play an important role in the handling of a number of endogenous and exogenous anionic substances in the kidney. In this study, we investigated prostaglandin E-2 (PGE(2)) transport properties and intrarenal localization of mouse organic anion transporter 3 (mOat3). When expressed in Xenopus oocytes, mOat3 mediated the time- and concentration-dependent transport of PGE(2) (K-m: 1.48 mu M). PGE(2) transport mediated by mOat3 was trans-stimulated by intracellular glutarate injected into the oocytes. PGE(2) efflux via mOat3 was also trans-stimulated by extracellular glutarate. Thus, mOat3 was shown to mediate the bidirectional transport of PGE(2), partly coupled to the dicarboxylate exchange mechanism. Immunohistochemical study revealed that mOat3 protein was localized at the basolateral membrane of renal proximal and distal tubules. Furthermore, diffuse expression of mOat3, including expression in the basolateral membrane in macula densa (MD) cells, was observed. These results indicate that mOat3 plays an important role as a basolateral transport pathway of PGE(2) in the distal nephron including MD cells that may constitute one of the indispensable steps for renin release and regulation of the tubuloglomerular feedback mechanism.