A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter
A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter
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DOI：
10.1152/ajpcell.00015.2012
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发表时间：
2012-06-01
影响因子：
5.5
通讯作者：
Moriyama, Yoshinori
中科院分区：
文献类型：
--
作者：
Togawa, Natsuko;Miyaji, Takaaki;Moriyama, Yoshinori
张文忠，张文忠. Na+磷酸盐协同转运蛋白同系物（SLC17A4蛋白）是肠有机阴离子输出蛋白。Am J Physiol Cell Physiol 302：C1652-C1660，2012.首次发表于2012年3月28日; doi：10.1152/ajpcell.00015.2012。SLC17阴离子转运蛋白家族包括9个成员，其以膜电位（Δ psi）-和Cl-依赖性方式转运各种有机阴离子。虽然大多数成员的转运底物和生理相关性已经确定，但对已知为Na +-磷酸盐协同转运蛋白同源物（NPT同源物）的SLC17A4蛋白知之甚少。在本研究中，我们研究了人SLC17A4蛋白的表达和转运特性。使用特异性抗体，我们发现，人类NPT同源物是专门表达和存在于肠道刷状缘膜。含有纯化蛋白质的蛋白脂质体以Cl-依赖的方式吸收放射性标记的对氨基马尿酸（PAH），代价是质子的电化学梯度，特别是Δ psi，穿过膜。Delta psi-和Cl-依赖的PAH摄取被SLC 17家族成员的常见抑制剂二异硫氰基二苯乙烯-2，2'-二磺酸和伊文思蓝抑制。顺式抑制研究表明，各种阴离子化合物，如亲水性非甾体抗炎药，普伐他汀，尿酸盐抑制PAH的摄取。蛋白脂质体吸收放射性标记的尿酸盐，其吸收具有与PAH吸收相似的性质。这些结果有力地表明，人类NPT同源物在肠道中充当多特异性有机阴离子输出者。由于SLC17A1蛋白（NPT1）和SLC17A3蛋白（NPT4）是负责肾脏尿酸盐挤出，我们的研究结果揭示了可能参与的NPT同源物在尿酸盐从肠道排出。
Togawa N, Miyaji T, Izawa S, Omote H, Moriyama Y. A Na+ phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter. Am J Physiol Cell Physiol 302: C1652-C1660, 2012. First published March 28, 2012; doi:10.1152/ajpcell.00015.2012.-The SLC17 anion transporter family comprises nine members that transport various organic anions in membrane potential (Delta psi)- and Cl- dependent manners. Although the transport substrates and physiological relevance of the majority of the members have already been determined, little is known about SLC17A4 proteins known to be Na+-phosphate cotransporter homologue (NPT homologue). In the present study, we investigated the expression and transport properties of human SLC17A4 protein. Using specific antibodies, we found that a human NPT homologue is specifically expressed and present in the intestinal brush border membrane. Proteoliposomes containing the purified protein took up radiolabeled p-aminohippuric acid (PAH) in a Cl--dependent manner at the expense of an electrochemical gradient of protons, especially Delta psi, across the membrane. The Delta psi- and Cl--dependent PAH uptake was inhibited by diisothiocyanostilbene-2,2'-disulfonic acid and Evans blue, common inhibitors of SLC17 family members. cis-Inhibition studies revealed that various anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs, pravastatin, and urate inhibited the PAH uptake. Proteoliposomes took up radiolabeled urate, with the uptake having properties similar to those of PAH uptake. These results strongly suggested that the human NPT homologue acts as a polyspecific organic anion exporter in the intestines. Since SLC17A1 protein (NPT1) and SLC17A3 protein (NPT4) are responsible for renal urate extrusion, our results reveal the possible involvement of a NPT homologue in urate extrusion from the intestinal duct.