Multidrug resistance proteins affect drug transmission across the placenta.
OBJECTIVE
We studied the role of multidrug resistance proteins in regulating transplacental transmission of corticosteroids and protease inhibitors.


METHODS
We performed quantitative polymerase chain reaction and FACS analyses to study MDR1 (encodes P-glycoprotein) and MRP-1 expression in extravillous (HTR-8/SVneo) and villous (BeWo) trophoblast cells treated with saquinavir, a multidrug resistance protein substrate. We measured H3-dexamethasone and H3-ritonavir transfer across confluent, syncytialized BeWo cells before and after treatment with agents that inhibit multidrug resistance proteins.


RESULTS
Compared with baseline expression, messenger RNA and protein levels were increased significantly in trophoblast cells after treatment with saquinavir. H3-dexamethasone and H3-ritonavir levels increased in BeWo cells after treatment with anti-P-glycoprotein antibodies or cyclosporine A. Transfer of H3-labeled drugs from the apical (eg, maternal) to basolateral (eg, fetal) side of the syncytialized BeWo cell monolayer was increased significantly when cells were pretreated with anti-P-glycoprotein antibodies.


CONCLUSIONS
Multidrug resistance proteins regulate drug levels in trophoblast cells and may mediate transmission of therapeutic agents across the placenta.
Parry
Samuel
S
Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Zhang
Jian
J
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D021041:Placental Circulation / Q000187:drug effects; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology*; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology; D014327:Trophoblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003907:Dexamethasone; D005938:Glucocorticoids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011480:Protease Inhibitors; D019438:Ritonavir; D019258:Saquinavir; C421109:multidrug resistance-associated protein 1