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- W2004623775 abstract "Drug cerebral pharmacokinetics may be altered in the case of inflammatory diseases. This may be due to a modification of drug transport through the blood–brain barrier, in particular through drug interaction with the membrane efflux transporter, P-glycoprotein. The objective of this study was to investigate the influence of the inflammatory cytokine, tumor necrosis factor (TNF)-α, on the functionality and expression of P-glycoprotein, and on mdr1a and mdr1b mRNA expression in immortalised rat brain endothelial cells, GPNT. Cells were treated with TNF-α for 4 days. Levels of mdr1a and mdr1b mRNAs were quantitated using real-time RT-PCR analysis and expression of P-glycoprotein was analyzed by Western blot. The functionality of P-glycoprotein was studied by following the accumulation of [3H]vinblastine in the cells without and with a pre-treatment with a P-glycoprotein inhibitor, GF120918. TNF-α increased the levels of mdr1a and mdr1b mRNAs while no effect was observed on protein expression. TNF-α increased [3H]vinblastine accumulation indicating a time and concentration-dependent decrease of P-glycoprotein activity. This effect was eliminated when the cells were pre-treated with GF120918. Our observation of a decrease in P-glycoprotein activity could suggest that in the case of inflammatory diseases, brain delivery of P-glycoprotein-dependent drugs can be enhanced." @default.
- W2004623775 created "2016-06-24" @default.
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- W2004623775 date "2003-08-01" @default.
- W2004623775 modified "2023-10-18" @default.
- W2004623775 title "Influence of tumor necrosis factor-α on the expression and function of P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT" @default.
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- W2004623775 doi "https://doi.org/10.1016/s0006-2952(03)00340-x" @default.
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