Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3
Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3
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DOI：
10.1007/s004240100697
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发表时间：
2001-11-01
影响因子：
4.5
通讯作者：
Hagenbuch, B
中科院分区：
文献类型：
--
作者：
Cattori, V;van Montfoort, JE;Hagenbuch, B
有机阴离子转运多肽(啮齿动物：OATPs。人：OATP)参与吸收和消除各种结构上无关的两亲性有机化合物。该蛋白家族的几个成员通过肝细胞的基底膜介导底物的摄取，作为肝脏消除的第一步。与Oatp1和Oatp2的特性不同，最近克隆的Oatp4的定位和底物特异性还没有得到详细的研究。因此，我们提出了针对Oatp4 C末端的抗体，并将这个85 kDa的蛋白定位于大鼠肝细胞的基底膜。与Oatp1和Oatp2类似，Oatp4是一种高亲和力的多特异性转运蛋白。脱氢表雄酮硫酸盐、白三烯C-4和阴离子多肽。此外，我们比较了Oatp4和Oatp3的底物特异性，到目前为止，Oatp3主要被证明介导肠道胆汁酸的转运。Oatp3具有相似的广泛底物专一性，但总体上比Oatp4亲和力低得多。因此，虽然Oatp4似乎与Oatp1和Oatp2在大鼠肝细胞的基底膜上协同工作，但Oatp3在小肠是一个多特异性的转运系统。
Organic anion transporting polypeptides (rodents: Oatps. human: OATPs) are involved in the absorption and elimination of a wide variety of structurally unrelated amphipathic organic compounds. Several members of this protein family mediate the uptake of substrates across the basolateral membrane of hepatocytes as the first step in hepatic elimination. In contrast to the well-characterized Oatp1 and Oatp2, the localization and substrate specificity of the recently cloned Oatp4 have not been investigated in detail. Therefore, we raised an antibody against the C-terminal end of Oatp4 and localized this 85-kDa protein to the basolateral membrane of rat hepatocytes. Similar to Oatp1 and Oatp2, Oatp4 is a multispecific transporter with high affinities for bromosulfophthalein. dehydroepiandrosterone sulfate, leukotriene C-4, and anionic peptides. In addition, we compared the substrate specificity of Oatp4 to that of Oatp3, which so far has mainly been shown to mediate intestinal bile acid transport. Oatp3 had a similar broad substrate specificity, but in general much lower affinities than Oatp4. Thus, while Oatp4 seems to work in concert with Oatp1 and Oatp2 in the basolateral membrane of rat hepatocytes, Oatp3 is a multispecific transport system in the small intestine.