Cattori V, van Montfoort J E, Stieger B, Landmann L, Meijer D K, Winterhalter K H, Meier P J, Hagenbuch B
Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, 8091 Zurich, Switzerland.
Pflugers Arch. 2001 Nov;443(2):188-95. doi: 10.1007/s004240100697.
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 C4, 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.
有机阴离子转运多肽（啮齿动物：Oatps；人类：OATPs）参与多种结构不相关的两亲性有机化合物的吸收和消除。该蛋白家族的几个成员介导底物跨肝细胞基底外侧膜的摄取，这是肝脏消除过程的第一步。与已得到充分表征的Oatp1和Oatp2不同，最近克隆的Oatp4的定位和底物特异性尚未得到详细研究。因此，我们制备了一种针对Oatp4 C末端的抗体，并将这种85 kDa的蛋白定位到大鼠肝细胞的基底外侧膜。与Oatp1和Oatp2相似，Oatp4是一种多特异性转运体，对溴磺酞、硫酸脱氢表雄酮、白三烯C4和阴离子肽具有高亲和力。此外，我们将Oatp4的底物特异性与Oatp3的底物特异性进行了比较，到目前为止，Oatp3主要被证明介导肠道胆汁酸转运。Oatp3具有相似的广泛底物特异性，但总体亲和力比Oatp4低得多。因此，虽然Oatp4似乎在大鼠肝细胞基底外侧膜中与Oatp1和Oatp2协同发挥作用，但Oatp3是小肠中的一种多特异性转运系统。
