MODULATION OF P-GLYCOPROTEIN ACTIVITY BY GLIAL FACTORS AND RETINOIC ACID IN AN IMMORTALIZED RAT-BRAIN MICROVESSEL ENDOTHELIAL-CELL LINE

P-glycoprotein (P-gp), a product of the multidrug-resistant (mdr) gene s, is expressed in the endothelial cells of the blood-brain barrier (B BB). 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 col chicine. When RBE4 cells were cultured either in the presence of CG-co nditioned medium or on C6- or astrocyte-extracellular matrix, intracel lular vinblastine and colchicine concentrations were decreased. When t he cells were treated with RA, increases in P-gp activities were corre lated with increases in P-gp levels. Effects of simultaneous treatment s with glial factors and RA were studied in RBE4 cells cultured on ast rocyte-extracellular matrix and were shown to be additive on P-gp acti vity and level. RBE4 cells may serve as a useful in vitro model for ba sic research on P-gp regulation at the level of the BBB. (C) 1997 Else vier Science Ireland Ltd.