Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus
Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus
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DOI：
10.1124/mol.61.5.982
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发表时间：
2002-05-01
影响因子：
3.6
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
--
作者：
Nagata, Y;Kusuhara, H;Sugiyama, Y
我们以前报道过青霉素(PCG)的高效外排系统位于脉络丛(CP)。在这项研究中，我们研究了大鼠有机阴离子转运体1(rOat1；S/c22a6)和rOat3(S/c22a8)在CP摄取PCG和对氨基马尿酸(PAH)中的作用。免疫组织化学染色显示rOat3定位于脉络膜上皮细胞刷状缘膜。PCG和PAH被分离的大鼠CP摄取，K-m值分别为111和354微米。一项相互抑制的研究表明，同一转运体对分离的大鼠CP摄取PCG和PAH负责。通过检测有机阴离子和西咪替丁对其摄取的影响，证实了这一点。雌二醇-17β-葡萄糖醛酸苷和西咪替丁是rOat3的选择性抑制剂。雌激素-17β-葡萄糖醛酸苷和西咪替丁对大鼠CP摄取PAH和PCG的抑制常数相当。此外，这些值也与rOat3的值相当，但与rOat1的值不同。这些结果表明，rOat3主要负责大鼠脑脊液对PCG和PAH的摄取，并通过清除脑脊液中的底物对脑脊液起解毒作用。
We reported previously that an efficient efflux system for benzylpenicillin (PCG) is located on the choroid plexus (CP). In this study, we investigated the involvement of rat organic anion transporter 1 (rOat1; S/c22a6) and rOat3 (S/c22a8) in the uptake of PCG and p-aminohippurate (PAH) by the CP. Western blot analysis indicates the expression of rOat3, but not rOat1, on the CP, and immunohistochemical staining shows that rOat3 is localized on the brush border membrane of the choroid epithelial cells. PCG and PAH were found to be taken up by isolated rat CP, with K-m values of 111 and 354 muM, respectively. A mutual inhibition study suggests that the same transporter is responsible for the uptake of PCG and PAH by isolated rat CP. This was confirmed by examining the effect of organic anions and cimetidine on their uptake. Estradiol-17beta-glucuronide and cimetidine were found to be selective inhibitors of rOat3. The inhibition constants of the inhibitors including estradiol-17beta-glucuronide and cimetidine were comparable for the uptake of PAH and PCG by isolated rat CP. In addition, these values were also comparable with those for rOat3, but not with those for rOat1. These results suggest that rOat3 is mainly responsible for the uptake of PCG and PAH by isolated rat CP, and it functions as one of the detoxification systems on the CP by removing its substrates from the cerebrospinal fluid.