Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells

被引:118
作者
Zhang, Y
Schuetz, JD
Elmquist, WF
Miller, DW
机构
[1] Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Pfizer Global Res & Dev, PDM Dept, Ann Arbor, MI USA
[3] St Jude Childrens Res Hosp, Dept Pharmacol, Memphis, TN USA
[4] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA
关键词
D O I
10.1124/jpet.104.068528
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Several multidrug resistance-associated protein (MRP) homologs are expressed in brain microvessel endothelial cells forming the blood-brain barrier (BBB). The influence of these MRP transporters on BBB permeability will be dependent on their localization within the brain microvessel endothelial cells. Using two different and complementary approaches, the localization of various MPR homologs (MRP1, MRP4, and MRP5) was examined in primary cultured bovine brain microvessel endothelial cells (BBMECs). The first approach involved centrifugal separation of apical and basolateral plasma membranes of cultured BBMECs. The membrane fractions were then subjected to Western blot analysis for MRPs. The second approach used confocal laser scanning microscopy to determine membrane localization of MRPs in BBMECs. Results show a predominantly apical plasma membrane distribution for MRP1 and MRP5, and an almost equal distribution of MRP4 on the apical and basolateral plasma membrane of BBMECs. These studies provide the first demonstration of the localization of MRP1, MRP4, and MRP5 homologs in brain microvessel endothelial cells. The present studies also indicate that the localization of MRPs in the endothelial cells forming the BBB is different from that observed in polarized epithelial cells and thus may contribute to the reduced entry and enhanced elimination of organic anions and nucleotides in the brain.
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收藏
页码:449 / 455
页数:7
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