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

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Atkinson DE, Greenwood SL, Sibley CP, Glazier JD, Fairbairn LJ

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

Am J Physiol Cell Physiol. 2003 Sep;285(3):C584-91. Epub 2003 Apr 30.

PubMed ID

12724138 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Vinblastine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor Inducer	Details