Multidrug resistance proteins affect drug transmission across the placenta.

Abstract:

OBJECTIVE:We studied the role of multidrug resistance proteins in regulating transplacental transmission of corticosteroids and protease inhibitors. STUDY DESIGN: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. CONCLUSION:Multidrug resistance proteins regulate drug levels in trophoblast cells and may mediate transmission of therapeutic agents across the placenta.

journal_name

Am J Obstet Gynecol

authors

Parry S,Zhang J

doi

10.1016/j.ajog.2007.02.019

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

476.e1-6

issue

5

eissn

0002-9378

issn

1097-6868

pii

S0002-9378(07)00253-0

journal_volume

196

pub_type

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