Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood–brain barrier

The aim of the present study was to investigate the expression of nuclear receptor mRNA and regulation of the expression of ATP-binding cassette (ABC) transporters by nuclear receptor agonists in rat brain capillary endothelial cells, which form the blood–brain barrier, by using rat brain capillary fraction from 8-week-old rats and a conditionally immortalized brain capillary endothelial cell line (TR-BBB13). RT-PCR analysis revealed that liver X receptor α and β, retinoid X receptor α and β and peroxisome proliferator-activating receptor α and β mRNAs were expressed in the rat brain capillary endothelial cells and TR-BBB cells. In contrast, pregnane X receptor, farnesoid X receptor and constitutive androstane receptor were not detected. Furthermore, treatment with a liver X receptor agonist increased the ABCA1 mRNA level in TR-BBB13 cells, while ABCG2 mRNA expression was not affected. Treatment with a rat pregnane X receptor agonist did not affect the ABCB1 mRNA level in TR-BBB13 cells. These results demonstrate that the rat blood–brain barrier has an expressional regulation mechanism via sterol-related nuclear receptor, and indicate that the blood–brain barrier in 8-week-old rats lacks ABCB1 regulation via pregnane X receptor.