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Am J Physiol Cell Physiol 285: C584-C591, 2003. First published April 30, 2003; doi:10.1152/ajpcell.00418.2002
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer

Diane E. Atkinson,1 Susan L. Greenwood,1 Colin P. Sibley,1 Jocelyn D. Glazier,1 and Leslie J. Fairbairn2

1Academic Unit of Child Health, University of Manchester, St Mary's Hospital, Manchester M13 OJH; and 2Paterson Institute of Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom

Submitted 9 September 2002 ; accepted in final form 24 April 2003

Natural differences in expression and retroviral transduction techniques were used to test the hypothesis that MDR1 P-glycoprotein (P-gp) and MRP1 (multidrug resistance-related protein) contribute to xenobiotic handling by placental trophoblast. RT-PCR and Western blotting in placenta, primary cytotrophoblast cell cultures, and BeWo, JAr, and JEG choriocarcinoma cell lines showed that MRP1 was ubiquitously expressed, whereas MDR1 was absent or minimally expressed in BeWo and JEG cell lines. In syncytiotrophoblast, P-gp was localized predominantly to the microvillous, maternal facing plasma membrane, and MRP1 to the basal, fetal facing plasma membrane. Functional studies showed that cyclosporin A-sensitive accumulation of [3H]vinblastine by cells containing both transport proteins was significantly different from those expressing predominantly MRP1. Retroviral gene transfer of MDR1 to BeWo cells confirmed that this difference was due to the relative expression of MDR1. Therefore, both P-gp and MRP1 contribute to xenobiotic handling by the trophoblast. Localization of P-gp to the microvillous membrane suggests an essential role in preventing xenobiotic accumulation by the syncytiotrophoblast and, therefore, in protecting the fetus.

placenta; multidrug resistance; xenobiotic


Address for reprint requests and other correspondence: D. E. Atkinson, Academic Unit of Child Health, Univ. of Manchester, St Mary's Hospital, Hathersage Rd., Manchester M13 OJH, United Kingdom (E-mail: diane.e.atkinson{at}man.ac.uk).




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