Expression of members of the multidrug resistance protein family in human term placenta.
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.
St-Pierre
M V
MV
Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland. st-pierre@kpt.unizh.ch
Serrano
M A
MA
Macias
R I
RI
Dubs
U
U
Hoechli
M
M
Lauper
U
U
Meier
P J
PJ
Marin
J J
JJ
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis / Q000235:genetics*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D018432:Drug Resistance, Multiple; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006000:Glycocholic Acid / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D005978:Glutathione; D006000:Glycocholic Acid; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; C000715087:ABCC2 protein, human; C078444:MSH3 protein, human; C030190:S-(2,4-dinitrophenyl)glutathione; C421109:multidrug resistance-associated protein 1