Modulation of P-glycoprotein activity by glial factors and retinoic acid in an immortalized rat brain microvessel endothelial cell line

被引:46
作者
ElHafny, B
Chappey, O
Piciotti, M
Debray, M
Boval, B
Roux, F
机构
[1] HOP FERNAND WIDAL,INSERM U26,UNITE NEUROPHARMACONUTR,F-75475 PARIS 10,FRANCE
[2] HOP LARIBOISIERE,LAB BIOL VASCULAIRE & CELLULAIRE,F-75010 PARIS,FRANCE
关键词
blood-brain barrier; glial factors; P-glycoprotein; retinoic acid; immortalized cells;
D O I
10.1016/S0304-3940(97)00679-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
P-glycoprotein (P-gp), a product of the multidrug-resistant (mdr) genes, is expressed in the endothelial cells of the blood-brain barrier (BBB). Effects of glial factors and retinoic acid (RA) on P-gp activity and level were investigated in the immortalized rat brain endothelial cell line RBE4, which expressed immunodetectable P-gp associated with a decrease in accumulation of the P-gp substrates, vinblastine and colchicine. When RBE4 cells were cultured either in the presence of CG-conditioned medium or on C6- or astrocyte-extracellular matrix, intracellular vinblastine and colchicine concentrations were decreased. When the cells were treated with RA, increases in P-gp activities were correlated with increases in P-gp levels. Effects of simultaneous treatments with glial factors and RA were studied in RBE4 cells cultured on astrocyte-extracellular matrix and were shown to be additive on P-gp activity and level. RBE4 cells may serve as a useful in vitro model for basic research on P-gp regulation at the level of the BBB. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:107 / 111
页数:5
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