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Received for publication March 19, 2004.
Revised May 27, 2004.
Accepted for publication June 21, 2004.
Several multidrug resistance-associated protein (MRP) homologues 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 homologues (MRP1, MRP4, and MRP5) was examined in primary cultured bovine brain microvessel endothelial cells (BBMEC). The first approach involved centrifugal separation of apical and basolateral plasma membranes of cultured BBMEC. 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 BBMEC. 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 BBMEC. These studies provide the first demonstration of the localization of MRP1, MRP4, and MRP5 homologues in brain microvessel endothelial cells. The present studies also indicate that the localization of MRPs in the endothelial cells forming the BBB is different than 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.
Key words:
blood-brain barrier, brain endothelial cell, confocal microscopy, drug efflux transporter, membrane localization, multidrug resistance-associated protein
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