Involvement of rat organic anion transporter 3 in the uptake of an organic herbicide, 2,4-Dichlorophenoxyacetate, by the isolated rat choroid plexus
Involvement of rat organic anion transporter 3 in the uptake of an organic herbicide, 2,4-Dichlorophenoxyacetate, by the isolated rat choroid plexus
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DOI：
10.1002/jps.20175
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发表时间：
2004-11-01
影响因子：
3.8
通讯作者：
Sugiyama, Y
中科院分区：
文献类型：
--
作者：
Nagata, Y;Kusuhara, H;Sugiyama, Y
2，4-二氯苯氧乙酸（2，4-D）是一种阴离子除草剂。本研究的目的是研究是否有机阴离子转运蛋白3（Oat 3; Slc 22 a8）是唯一负责的2，4-D的摄取由离体大鼠脉络丛（CP）。当在LLC-PK 1细胞中表达时，rOat 3主要定位于基底外侧膜。虽然在对照LLC-PK 1细胞中没有2，4-D的载体转运，但rOat 3的表达使2，4-D的基底至顶端转运增加了四倍，而不影响相反方向的跨细胞转运。2，4-D在rOat 3-LLC中的基部至顶端转运是饱和的，K-m值为20 μ M。用离心过滤法测定了大鼠CP对2，4-D的摄取。在分离的大鼠CP中观察到2，4-D的饱和摄取，K-m值为22 μ M。丙磺舒和底物rOat 3，如对氨基马尿酸，青霉素，西咪替丁，抑制2，4-D的摄取由分离的大鼠CP。它们的Ki值与分离的大鼠CP摄取苄青霉素的Ki值相当，这主要是由rOat 3介导的。此外，苄青霉素是一个竞争性抑制剂的摄取2，4-D的分离大鼠CP。这些结果表明，2，4-D和苄青霉素共享相同的转运体为他们的摄取分离的大鼠CP，和rOat 3是最有可能的候选转运体。(C)2004 Wiley-Liss，Inc.和美国药剂师协会
2,4-Dichlorophenoxyacetic acid (2,4-D) is an anionic herbicide. The purpose of the present study is to examine whether organic anion transporter 3 (Oat3; Slc22a8) is solely responsible for the uptake of 2,4-D by the isolated rat choroid plexus (CP). When expressed in LLC-PK1 cells, rOat3 was mainly localized to the basolateral membrane. Although there was no vectorial transport of 2,4-D in the control LLC-PK1 cells, expression of rOat3 increased the basal-to-apical transport of 2,4-D fourfold without a affecting the transcellular transport in the opposite direction. The basal-to-apical transport of 2,4-D in rOat3-LLC was saturable with a K-m value of 20 muM. The uptake of 2,4-D by the isolated rat CP was determined using the centrifugal filtration method. Saturable uptake of 2,4-D was observed in the isolated rat CP with a K-m value of 22 muM. Probenecid and substrates of rOat3, such as p-aminohippurate, benzylpenicillin, and cimetidine, inhibited the uptake of 2,4-D by the isolated rat CP. Their K-i values were comparable with those for the uptake of benzylpenicillin by the isolated rat CP, which is mainly mediated by rOat3. Furthermore, benzylpenicillin was a competitive inhibitor for the uptake of 2,4-D by the isolated rat CP. These results suggest that 2,4-D and benzylpenicillin share the same transporter for their uptake by the isolated rat CP, and rOat3 is the most likely candidate transporter. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.