Drug transporters in the human blood-placental barrier.
Studies on the increasing number of transporters found in the placental barrier are gaining momentum, because of their tissue-specific expression, significance in physiology and disease, and the possible utilization of the emerging knowledge in pharmacology. In the placenta, both syncytiotrophoblast and fetal capillary endothelium express transporters. Fetal exposure is determined by the net effect of combination of transporters, their nature and localization in relation to placental cells and their substrate specificity. Although the significance of placental transporters on human fetal drug exposure is almost an unstudied field so far, their potential use to design drugs that do not cross the placenta is already being pursued. It is thus of interest to review the existing knowledge of human placental transporters. Transporters in all groups which take part in drug transport are found in human placenta. Especially, ATP-binding cassette transporters ABCG2/breast cancer resistance protein, ABCB1/P-glycoprotein and ABCC2/MRP2 are all expressed at the apical surface of syncytiotrophoblast facing maternal blood and are putatively important protective proteins both for placental tissue and the fetus, because they are efflux transporters and their substrates include many drugs and also environmental chemicals. Such protective effect has been shown in animals, but these results cannot be directly extrapolated to humans due to interspecies differences in placental structure and function. Experimental models utilizing human placental tissue, especially human placental perfusion, offer valuable possibilities, which have been insufficiently studied so far.
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland. kirsi.vahakangas@uku.fi
Kirsi
K
Vähäkangas
Päivi
P
Myllynen
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D000089762:Multidrug Resistance-Associated Protein 2; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism*; D011247:Pregnancy
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D004364:Pharmaceutical Preparations