Abstract
The ABC drug transporters in the placenta are involved in controlling the exchange of endogenous and exogenous moieties. PXR is a nuclear receptor which regulates the hepatic expression of several key ABC transporters but it is unclear whether PXR is involved in the regulation of these transporters in the placenta. This study explores the role of PXR in the regulation of placental drug transporters. The placental expression of Mdr1a, Bcrp, Mrp1, 2 and 3 was examined in PXR knockouts (-/-), heterozygote (+/-) and wildtype (+/+) mice by quantitative PCR. The impact of PXR activation was examined in pregnant PCN-treated mice. As compared to controls, the basal expression of Mdr1a, Bcrp, Mrp1, 2 was significantly higher in (+/-) and (-/-) mice. Alterations in the expression of mdr1a, bcrp and mrp1-3 between GD 10 and GD 17 was dissimilar between +/+ and -/- mice. While PCN treatment induced maternal and fetal hepatic expression of Cyp3a11; placental expression of transporters were not significantly changed. Overall, our results suggest a repressive role of PXR in the basal expression of several placental transporters and a tissue-specific induction of these target genes after PXR activation.
- Received June 22, 2010.
- Accepted December 1, 2010.
- The American Society for Pharmacology and Experimental Therapeutics