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

Abstract

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 alpha and beta, retinoid X receptor alpha and beta and peroxisome proliferator-activating receptor alpha and beta 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.