Transport of fluorescein in MDCKII-MRP1 transfected cells and mrp1-knockout mice.
Transport of fluorescein in MDCKII-MRP1 transfected cells and mrp1-knockout mice.
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MDCKII-MRP1 转染细胞和 mrp1 敲除小鼠中荧光素的转运。
DOI：
10.1006/bbrc.2001.5062
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Elmquist,WF
中科院分区：
文献类型：
--
作者：
Sun,H;Johnson,DR;Finch,RA;Sartorelli,AC;Miller,DW;Elmquist,WF
多药耐药相关蛋白1（MRP 1）是一种膜结合转运蛋白，参与有机阴离子的外排，并与癌症的多药耐药性有关。据报道，MRP 1在正常组织中普遍表达，包括大脑。在血脑屏障和血CSF屏障中存在功能性有机阴离子转运体，其影响各种化合物向脑的分布，这早已为人们所知。本研究的目的是研究MRP 1在模型有机阴离子荧光素脑分布中的作用。最初通过检查MDCKII MRP 1转染细胞中荧光素的积累来确定MRP 1对荧光素的底物特异性。然后在野生型和mrp 1基因敲除小鼠中检查荧光素在脑中的分布。结果表明，在MDCKII MRP 1转染细胞中，荧光素的积累比野生型MDCKII细胞中的荧光素的积累显著降低（约低40%）。MRP 1抑制剂如丙磺舒、MK-571和LY 402913在MDCKII MRP 1转染细胞中比在野生型MDCKII细胞中更大程度地增强荧光素积累。在一项体内研究中，静脉注射荧光素后，mrp 1基因敲除小鼠的荧光素脑-血浆浓度比与野生型小鼠没有显著差异。然而，当丙磺舒与荧光素在野生型小鼠中共同给药时，荧光素脑-血浆比率显著增加（1.5倍）。这些发现表明荧光素是MRP 1的底物。此外，体内研究还表明，MRP 1在荧光素在脑中的转运和分布中的作用有限。因此，其他有机阴离子转运蛋白，包括MRP家族的各种亚型，可能负责脑中有机阴离子的积累和转运。
The multidrug resistant-associated protein 1 (MRP1) is a membrane-bound transport protein that is involved in the efflux of organic anions and has been implicated in multidrug resistance in cancer. MRP1 has also been reported to be ubiquitously expressed in normal tissues, including the brain. The presence of functional organic anion transporters in the blood–brain and blood–CSF barriers that influence the distribution of various compounds to the brain has long been known. The purpose of this study was to examine the role of MRP1 in the brain distribution of a model organic anion, fluorescein. The substrate specificity of MRP1 for fluorescein was initially determined by examining the accumulation of fluorescein in MDCKII MRP1-transfected cells. The distribution of fluorescein in the brain was then examined in wild-type and mrp1 gene knockout mice. The results show that in MDCKII MRP1-transfected cells, the accumulation of fluorescein was significantly lower (about 40% lower) than that in wild-type MDCKII cells. MRP1 inhibitors such as probenecid, MK-571, and LY402913 enhanced fluorescein accumulation in MDCKII MRP1-transfected cells to a greater extent than in wild-type MDCKII cells. In an in vivo study, after intravenous injection of fluorescein, the fluorescein brain-to-plasma concentration ratio in mrp1 knockout mice was not significantly different than that in wild-type mice. However, when probenecid was co-administered with fluorescein in wild-type mice, the fluorescein brain-to-plasma ratio was significantly increased (1.5-fold). These findings suggest that fluorescein is a substrate for MRP1. Furthermore, the in vivo study also suggests that MRP1 has a limited role in the transport and distribution of fluorescein in the brain. Therefore, other organic anion transport proteins, including the various isoforms of the MRP family, may be responsible for the accumulation and transport of organic anions in the brain.
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影响因子：
11.2
作者：
A. Lorico;G. Rappa;R. A. Finch;Di Yang;R. A. Flavell;Alan C. Sartorelli
通讯作者：
A. Lorico;G. Rappa;R. A. Finch;Di Yang;R. A. Flavell;Alan C. Sartorelli
DOI：
--
发表时间：
2000-06
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
E. Choo;B. Leake;C. Wandel;H. Imamura;A. J. Wood;G. Wilkinson;R. Kim
通讯作者：
E. Choo;B. Leake;C. Wandel;H. Imamura;A. J. Wood;G. Wilkinson;R. Kim
DOI：
--
发表时间：
2001-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
E. Batrakova;Donald W. Miller;Shu Li;V. Alakhov;A. Kabanov;W. Elmquist
通讯作者：
E. Batrakova;Donald W. Miller;Shu Li;V. Alakhov;A. Kabanov;W. Elmquist
多重耐药 mdr1a/1b 和 mrp1 缺陷小鼠的药理学表型。
影响因子：
11.2
作者：
Dennis R. Johnson;R. A. Finch;Z. Lin;Caroline J. Zeiss;Alan C. Sartorelli
通讯作者：
Alan C. Sartorelli
MRP 在人体组织和成人实体瘤细胞系中的表达模式。
DOI：
10.1093/jnci/87.16.1256
发表时间：
1995
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Kruh,GD;Gaughan,KT;Godwin,A;Chan,A
通讯作者：
Chan,A