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
- 1 May 2003
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 371 (3), 897-905
- https://doi.org/10.1042/bj20030034
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.Keywords
This publication has 33 references indexed in Scilit:
- Affinity of Human Serum Albumin for Bilirubin Varies with Albumin Concentration and Buffer CompositionJournal of Biological Chemistry, 2001
- Hepatic Uptake of Bilirubin and Its Conjugates by the Human Organic Anion Transporter SLC21A6Journal of Biological Chemistry, 2001
- Antibody Reaction Patterns in First Trimester Placenta: Implications for Trophoblast Isolation and Purity ScreeningPlacenta, 2000
- Expression of rat, renal NHE2 and NHE3 during postnatal developmentalBiochimica et Biophysica Acta (BBA) - Biomembranes, 2000
- Heme Oxygenase: Who Needs It?Proceedings of the Society for Experimental Biology and Medicine, 1999
- Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liverGastroenterology, 1995
- Age-Dependent Sensitivity of Cultured Rat Glial Cells to Bilirubin ToxicityExperimental Neurology, 1993
- Determinants of Bile Formation During Development: Ontogeny of Hepatic Bile Acid Metabolism and TransportSeminars in Liver Disease, 1987
- Differential sensitivity of neural cells to bilirubin toxicityExperimental Neurology, 1986
- Bilirubin binding in premature infants from birth to 3 months.Archives of Disease in Childhood, 1986