Affiliation:
1. Department of Physiology and Pharmacology, University of Salamanca, Salamanca 37007, Spain
2. Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain
3. Department of Physiology, University of Leon, Leon 24007, Spain
Abstract
Recent functional studies have suggested that, in addition to simple diffusion, carrier-mediated transport may play an important role in foetal unconjugated bilirubin (UCB) uptake by the placenta. We have investigated the role of organic anion-transporting polypeptides (OATPs) in UCB transport by the placenta–maternal liver tandem. RNA was obtained from human liver (hL), human placenta (hPl) at term, and purified (> 80%) cytokeratin-7-positive mononucleated human trophoblast cells (hTCs). By analytical reverse transcription (RT)-PCR, agarose gel electrophoresis separation and sequencing, the mRNA of OATP-A (SLC21A3) and OATP-8 (SLC21A8) was identified in hL, hPl and hTCs, whereas that of OATP-C (SLC21A6) was detectable only in hL. Real-time quantitative RT-PCR revealed that in hL the abundance of mRNA was OATP-8 > OATP-C ≫ OATP-A, whereas in hPl and hTCs this was OATP-8 ≫ OATP-A ≫ OATP-C. Expression levels for these OATPs were hL ≫ hTCs > hPl. Injection of mRNA of OATP-A, OATP-C or OATP-8 or RNA from hL, hPl or hTCs into Xenopus laevis oocytes conferred on them the ability to take up [3H]17β-d-glucuronosyl oestradiol ([3H]E217βG) and [3H]UCB, although in the case of OATP-A mRNA, the induced uptake of [3H]UCB was very low. Cis-inhibition of [3H]E217βG and [3H]UCB uptake by both unlabelled E217βG and UCB was found in all cases. The affinity and efficiency of [3H]UCB transport was OATP-C > OATP-8. Kinetic parameters for [3H]UCB uptake induced by RNA from hTCs resembled most closely those of OATP-8. In conclusion, our results suggest that OATP-8 may play a major role in the carrier-mediated uptake of foetal UCB by the placental trophoblast, whereas both OATP-8 and OATP-C may substantially contribute to UCB uptake by adult hepatocytes.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
152 articles.
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