Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin.

摘要: Recent functional studies have suggested that, in addition to simple diffusion, carrier-mediated transport may play an important role foetal unconjugated bilirubin (UCB) uptake by the placenta. We investigated of organic anion-transporting polypeptides (OATPs) UCB placenta-maternal liver tandem. RNA was obtained from human (hL), placenta (hPl) at term, and purified (> 80%) cytokeratin-7-positive mononucleated trophoblast cells (hTCs). By analytical reverse transcription (RT)-PCR, agarose gel electrophoresis separation sequencing, mRNA OATP-A ( SLC21A3 ) OATP-8 SLC21A8 identified hL, hPl hTCs, whereas that OATP-C SLC21A6 detectable only hL. Real-time quantitative RT-PCR revealed hL abundance > >> OATP-A, hTCs this OATP-C. Expression levels for these OATPs were hPl. Injection or into Xenopus laevis oocytes conferred on them ability take up [(3)H]17 beta-D-glucuronosyl oestradiol ([(3)H]E(2)17 beta G) [(3)H]UCB, although case mRNA, induced [(3)H]UCB very low. Cis -inhibition [(3)H]E(2)17 G both unlabelled E(2)17 found all cases. The affinity efficiency OATP-8. Kinetic parameters resembled most closely those In conclusion, our results suggest a major placental trophoblast, substantially contribute adult hepatocytes.