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- W2108641213 abstract "Xenobiotic efflux pumps at the blood-brain barrier are critical modulators of central nervous system pharmacotherapy. We previously found expression of the ligand-activated nuclear receptor, pregnane X receptor (PXR), in rat brain capillaries, and showed increased expression and transport activity of the drug efflux transporter, P-glycoprotein, in capillaries exposed to PXR ligands (pregnenolone-16alpha-carbonitrile (PCN) and dexamethasone) in vitro and in vivo. Here, we show increased protein expression and transport activity of another efflux pump, multidrug resistance-associated protein isoform 2 (Mrp2), in rat brain capillaries after in vitro and in vivo exposure to PCN and dexamethasone. The phase-II drug-metabolizing enzyme, glutathione S-transferase-pi (GSTpi), was found to be expressed in brain capillaries, where it colocalized to a large extent with Mrp2 at the endothelial cell luminal plasma membrane. Like Mrp2, GSTpi protein expression increased with PXR activation. Colocalization and coordinated upregulation suggest functional coupling of the metabolizing enzyme and efflux transporter. These findings indicate that, as in hepatocytes, brain capillaries possess a regulatory network consisting of nuclear receptors, metabolizing enzymes, and efflux transporters, which modulate blood-brain barrier function." @default.
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- W2108641213 date "2008-03-19" @default.
- W2108641213 modified "2023-10-16" @default.
- W2108641213 title "Coordinated Nuclear Receptor Regulation of the Efflux Transporter, Mrp2, and the Phase-Ii Metabolizing Enzyme, GSTπ, at the Blood—Brain Barrier" @default.
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- W2108641213 doi "https://doi.org/10.1038/jcbfm.2008.16" @default.
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