P-glycoprotein expression and distribution in the rat placenta during pregnancy

被引:61
作者
Novotna, M
Libra, A
Kopecky, M
Pavek, P [1 ]
Fendrich, Z
Semecky, V
Staud, F
机构
[1] Charles Univ, Dept Pharmacol & Toxicol, Fac Pharm Hradec Kralove, Prague, Czech Republic
[2] Charles Univ, Dept Biomed Sci, Fac Pharm Hradec Kralove, Prague, Czech Republic
关键词
P-glycoprotein; multidrug resistance; efflux transporter; placenta; rat; trophoblast;
D O I
10.1016/j.reprotox.2004.04.014
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
P-glycoprotein (P-gp) is a drug efflux transporter that limits the entry of various potentially toxic drugs and xenobiotics into the fetus and is thus considered a placental protective mechanism. In this study, P-gp expression was investigated in the rat chorioallantoic placenta over the course of pregnancy. Three methods have been employed: real-time RT-PCR, western blotting and immunohistochemistry. The expression of mdr1a and mdr1b genes was demonstrated as early as on the 11th gestation day (gd) and increased with advancing gestation. Western blotting analysis revealed the presence of P-gp in the rat placenta starting from gd 13 onwards. P-gp was localized in the developing labyrinth zone of the placenta on gd 13; from gd 15 up to the term P-gp was seen as a dot like continuous line in the syncytiotrophoblast layers. Our data confirm the presence of P-gp in the rat chorioallantoic placenta starting soon after its development, which may signify the involvement of P-gp in transplacental pharmacokinetics during the whole period of placental maturing. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:785 / 792
页数:8
相关论文
共 46 条
[21]   Drug-drug interaction mediated by inhibition and induction of P-glycoprotein [J].
Lin, JH .
ADVANCED DRUG DELIVERY REVIEWS, 2003, 55 (01) :53-81
[22]   Role of P-glycoprotein in pharmacokinetics - Clinical implications [J].
Lin, JH ;
Yamazaki, M .
CLINICAL PHARMACOKINETICS, 2003, 42 (01) :59-98
[23]   STAGE-SPECIFIC DISTRIBUTION OF P-GLYCOPROTEIN IN FIRST-TRIMESTER AND FULL-TERM HUMAN PLACENTA [J].
MACFARLAND, A ;
ABRAMOVICH, DR ;
EWEN, SWB ;
PEARSON, CK .
HISTOCHEMICAL JOURNAL, 1994, 26 (05) :417-423
[24]   Hormones and human trophoblast differentiation -: A review [J].
Malassiné, A ;
Cronier, L .
ENDOCRINE, 2002, 19 (01) :3-11
[25]   Activity and protein localization of multiple glutamate transporters in gestation day 14 vs. day 20 rat placenta [J].
Matthews, JC ;
Beveridge, MJ ;
Malandro, MS ;
Rothstein, JD ;
Campbell-Thompson, M ;
Verlander, JW ;
Kilberg, MS ;
Novak, DA .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 274 (03) :C603-C614
[26]  
METZ J, 1976, CELL TISSUE RES, V171, P305
[27]  
METZ J, 1978, CELL TISSUE RES, V192, P391
[28]   ON THE DEVELOPING RAT PLACENTA .1. DIFFERENTIATION AND JUNCTIONAL ALTERATIONS OF LABYRINTHINE LAYERS-II AND LAYERS-III [J].
METZ, J .
ANATOMY AND EMBRYOLOGY, 1980, 159 (03) :289-305
[29]   Sites of mRNA expression of the cystic fibrosis (CF) and multidrug resistance (MDR1) genes in the human placenta of early pregnancy:: No evidence for complementary expression [J].
Mylona, P ;
Hoyland, JA ;
Sibley, CP .
PLACENTA, 1999, 20 (5-6) :493-496
[30]   Expression of the cystic fibrosis (CF) and multidrug resistance (MDR1) genes during development and differentiation in the human placenta [J].
Mylona, P. ;
Glazier, J. D. ;
Greenwood, S. L. ;
Sides, M. K. ;
Sibley, C. P. .
MOLECULAR HUMAN REPRODUCTION, 1996, 2 (09) :693-698