PMID- 21127142
OWN - NLM
STAT- MEDLINE
DCOM- 20110614
LR  - 20181201
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 39
IP  - 3
DP  - 2011 Mar
TI  - Gestational and pregnane X receptor-mediated regulation of placental ATP-binding 
      cassette drug transporters in mice.
PG  - 465-71
LID - 10.1124/dmd.110.034983 [doi]
AB  - The ATP-binding cassette (ABC) drug transporters in the placenta are involved in 
      controlling the exchange of endogenous and exogenous moieties. Pregnane X 
      receptor (PXR) is a nuclear receptor that regulates the hepatic expression of 
      several key ABC transporters, but it is unclear whether PXR is involved in the 
      regulation of these transporters in the placenta. This study explores the role of 
      PXR in the regulation of placental drug transporters. The placental mRNA 
      expression of Mdr1a, Bcrp, and Mrp1, 2, and 3 was examined in PXR knockout (-/-), 
      heterozygote (+/-), and wild-type (+/+) mice by quantitative PCR. The impact of 
      PXR activation was examined in pregnant pregnane-16alpha-carbonitrile (PCN)-treated 
      mice. Compared with that in controls, the basal expression of Mdr1a, Bcrp, Mrp1, 
      and Mrp2 was significantly higher in (+/-) and (-/-) mice. Alterations in the 
      expression of mdr1a, bcrp, and mrp1, 2, and 3 between gestational day (GD) 10 and 
      GD 17 was dissimilar between (+/+) and (-/-) mice. Although PCN treatment induced 
      maternal and fetal hepatic expression of Cyp3a11; placental expression of 
      transporters were not significantly changed. Overall, our results suggest a 
      repressive role of PXR in the basal expression of several placental transporters 
      and a tissue-specific induction of these target genes after PXR activation.
FAU - Gahir, Sarabjit S
AU  - Gahir SS
AD  - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
FAU - Piquette-Miller, Micheline
AU  - Piquette-Miller M
LA  - eng
GR  - FRN 57688/Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101202
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abcg2 protein, mouse)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Steroid)
RN  - 1434-54-4 (Pregnenolone Carbonitrile)
RN  - 9EI49ZU76O (multidrug resistance protein 3)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/genetics/*metabolism
MH  - Animals
MH  - Female
MH  - *Gene Expression Regulation, Developmental/drug effects
MH  - Liver/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multidrug Resistance-Associated Proteins/genetics/metabolism
MH  - Organ Specificity
MH  - Placenta/drug effects/*metabolism
MH  - Pregnancy
MH  - Pregnancy Proteins/genetics/*metabolism
MH  - Pregnane X Receptor
MH  - Pregnenolone Carbonitrile/pharmacology
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Steroid/agonists/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2010/12/04 06:00
MHDA- 2011/06/15 06:00
CRDT- 2010/12/04 06:00
PHST- 2010/12/04 06:00 [entrez]
PHST- 2010/12/04 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
AID - dmd.110.034983 [pii]
AID - 10.1124/dmd.110.034983 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2011 Mar;39(3):465-71. doi: 10.1124/dmd.110.034983. Epub 2010 
      Dec 2.