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Expression of members of the multidrug resistance protein family in human term placenta.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2000 Oct; Vol. 279 (4), pp. R1495-503. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B analysis
ATP Binding Cassette Transporter, Subfamily B, Member 1 analysis
ATP-Binding Cassette Transporters analysis
Cell Membrane metabolism
Cell Membrane ultrastructure
Cloning, Molecular
DNA-Binding Proteins analysis
Endothelium, Vascular metabolism
Female
Glutathione analogs & derivatives
Glutathione pharmacokinetics
Glycocholic Acid metabolism
Humans
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
MutS Homolog 3 Protein
Placenta cytology
Pregnancy
Reverse Transcriptase Polymerase Chain Reaction
Trophoblasts metabolism
ATP Binding Cassette Transporter, Subfamily B genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
ATP-Binding Cassette Transporters genetics
DNA-Binding Proteins genetics
Drug Resistance, Multiple
Membrane Transport Proteins
Placenta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6119
- Volume :
- 279
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 11004020
- Full Text :
- https://doi.org/10.1152/ajpregu.2000.279.4.R1495