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Am J Physiol Regul Integr Comp Physiol 279: R1495-R1503, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 4, R1495-R1503, October 2000

Expression of members of the multidrug resistance protein family in human term placenta

M. V. St-Pierre1, M. A. Serrano2, R. I. R. Macias2, U. Dubs1, M. Hoechli3, U. Lauper4, P. J. Meier1, and J. J. G. Marin2

Division of Clinical Pharmacology and Toxicology, Departments of 1 Internal Medicine and 4 Obstetrics, University Hospital and 3 Electron Microscopy Laboratory, University of Zürich, CH-8091 Zürich, Switzerland; and 2 Departments of Biochemistry and Physiology, School of Pharmacy, University of Salamanca, 37007 Salamanca, Spain

The placenta serves, in part, as a barrier to exclude noxious substances from the fetus. In humans, a single-layered syncytium of polarized trophoblast cells and the fetal capillary endothelium separate the maternal and fetal circulations. P-glycoprotein is present in the syncytiotrophoblast throughout gestation, consistent with a protective role that limits exposure of the fetus to hydrophobic and cationic xenobiotics. We have examined whether members of the multidrug resistance protein (MRP) family are expressed in term placenta. After screening a placenta cDNA library, partial clones of MRP1, MRP2, and MRP3 were identified. Immunofluorescence and immunoblotting studies demonstrated that MRP2 was localized to the apical syncytiotrophoblast membrane. MRP1 and MRP3 were predominantly expressed in blood vessel endothelia with some evidence for expression in the apical syncytiotrophoblast. ATP-dependent transport of the anionic substrates dinitrophenyl-glutathione and estradiol-17-beta -glucuronide was also demonstrated in apical syncytiotrophoblast membranes. Given the cellular distribution of these transporters, we hypothesize that MRP isoforms serve to protect fetal blood from entry of organic anions and to promote the excretion of glutathione/glucuronide metabolites in the maternal circulation.

placenta transport; human multidrug resistance protein 1; human multidrug resistance protein 2; human multidrug resistance protein 3


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