Estrogen receptor β signaling through phosphatase and tensin homolog/phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3 down-regulates blood-brain barrier breast cancer resistance protein
We demonstrate a pathway through which sustained, extended exposure to of 17-β-estradiol (E2) signals down-regulation of breast cancer resistance protein (BCRP) at the blood-brain barrier. Six-hour exposure of isolated rat and mouse brain capillaries to E2 reduced BCRP transport activity and BCRP monomer and dimer expression. Experiments with brain capillaries from estrogen receptor (ER)alpha and […]
Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation
We identified the prostaglandin E2 receptor, EP1, as a key factor in the signaling pathway that mediates seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier. In the rat pilocarpine model, status epilepticus significantly increased P-glycoprotein expression by 92 to 197% in the hippocampal hilus and granule cell layer as well as the piriform cortex. The […]
Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR
We studied functional similarities between pig and human pregnane X receptor (PXR). We used brain capillary endothelial cells from pig to study the effect of PXR activation on P-glycoprotein. To activate PXR, we used the PXR ligands, rifampicin, hyperforin, and pregnenolone-16alpha-carbonitrile (PCN), and measured abcb1 mRNA with quantitative polymerase chain reaction, P-glycoprotein expression with Western […]