Breast cancer resistance protein: mediating the trans-placental transfer of glyburide across the human placenta.

摘要: Members of the ATP-binding cassette (ABC) efflux transporter family, including P-glycoprotein (PGP), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) have been shown to be highly expressed in human placenta. Recent studies documented that oral hypoglycemic glyburide does not cross placenta an appreciable extent. Furthermore, trans-placental transfer has affected by either presence PGP inhibitor, verapamil or MRP indomethacin. Therefore, our objective was identify other placental ABC transporters potentially involved limiting fetus. [(3)H]-glyburide transport examined brush border vesicles absence specific inhibitors. Prepared were 70% oriented right-side-out demonstrated 25-27 fold enrichment as compared whole Functional significant increases intra-vesicular accumulation treated with BCRP novobiocin. In contrast, inhibition well did affect accumulation. This is first evidence clearly indicate preferentially transported BCRP, Our study also indicates likely effluxes substrates fetal maternal direction