Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.
Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.
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DOI：
10.1152/ajpgi.2000.279.6.g1188
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发表时间：
2000-12
期刊：
影响因子：
--
通讯作者：
H. C. Walters;A. Craddock;H. Fusegawa;M. Willingham;P. Dawson
中科院分区：
文献类型：
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作者：
H. C. Walters;A. Craddock;H. Fusegawa;M. Willingham;P. Dawson
克隆大鼠和小鼠有机阴离子转运多肽 (oatp) 亚型 3 (oatp3)，以进一步确定肠道胆汁酸转运系统的组成部分。在转染的 COS 细胞中，oatp3 介导不依赖 Na(+)、DIDS 抑制的牛磺胆酸盐摄取（米氏常数约为 30 µM）。甘氨酸结合的二羟基胆汁酸的 oatp3 介导的摄取率和亲和力最高。在稳定转染的极化 Madin-Darby 犬肾 (MDCK) 细胞中，oatp3 仅介导牛磺胆酸盐的顶端摄取。 RT-PCR 分析显示，大鼠小肠中表达 oatp3，但不表达 oatp1 或 oatp2。通过 RNase 保护测定，可以很容易地在小肠以及大脑、肺和视网膜中检测到 oatp3 mRNA。针对羧基末端的抗体将 oatp3 定位于大鼠空肠肠细胞的顶端刷状缘膜。小鼠oatp3基因定位于小鼠6号染色体的一个区域。该区域与人类染色体12p12同线，其中人类OATP-A基因被定位，表明啮齿动物oatp3与人类OATP-A是直系同源的。这些转运和表达特性表明，大鼠 oatp3 介导先前描述的近端小肠的阴离子交换驱动的胆汁酸吸收。
The rat and mouse organic anion-transporting polypeptides (oatp) subtype 3 (oatp3) were cloned to further define components of the intestinal bile acid transport system. In transfected COS cells, oatp3 mediated Na(+)-independent, DIDS-inhibited taurocholate uptake (Michaelis-Menten constant approximately 30 microM). The oatp3-mediated uptake rates and affinities were highest for glycine-conjugated dihydroxy bile acids. In stably transfected, polarized Madin-Darby canine kidney (MDCK) cells, oatp3 mediated only apical uptake of taurocholate. RT-PCR analysis revealed that rat oatp3, but not oatp1 or oatp2, was expressed in small intestine. By RNase protection assay, oatp3 mRNA was readily detected down the length of the small intestine as well as in brain, lung, and retina. An antibody directed to the carboxy terminus localized oatp3 to the apical brush-border membrane of rat jejunal enterocytes. The mouse oatp3 gene was localized to a region of mouse chromosome 6. This region is syntenic with human chromosome 12p12, where the human OATP-A gene was mapped, suggesting that rodent oatp3 is orthologous to the human OATP-A. These transport and expression properties suggest that rat oatp3 mediates the anion exchange-driven absorption of bile acids previously described for the proximal small intestine.