多药耐药蛋白影响药物通过胎盘的转运。

Multidrug resistance proteins affect drug transmission across the placenta.

作者信息

Parry Samuel, Zhang Jian

机构信息

Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

出版信息

Am J Obstet Gynecol. 2007 May;196(5):476.e1-6. doi: 10.1016/j.ajog.2007.02.019.

DOI:10.1016/j.ajog.2007.02.019

PMID:17466710

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.

摘要

目的

我们研究了多药耐药蛋白在调节皮质类固醇和蛋白酶抑制剂经胎盘转运中的作用。

研究设计

我们进行了定量聚合酶链反应和流式细胞术分析，以研究多药耐药蛋白底物沙奎那韦处理后的绒毛外（HTR-8/SVneo）和绒毛（BeWo）滋养层细胞中MDR1（编码P-糖蛋白）和MRP-1的表达。我们在使用抑制多药耐药蛋白的药物处理前后，测量了H3-地塞米松和H3-利托那韦在汇合、融合的BeWo细胞中的转运情况。