Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-14
pubmed:abstractText
Members of the ATP-binding cassette (ABC) efflux transporter family, including P-glycoprotein (PGP), the multidrug resistance-associated proteins (MRPs) and the breast cancer resistance protein (BCRP) have been shown to be highly expressed in the human placenta. Recent studies documented that the oral hypoglycemic glyburide does not cross the human placenta to an appreciable extent. Furthermore, the trans-placental transfer of glyburide has been shown not to be affected by either the presence of PGP inhibitor, verapamil or MRP inhibitor, indomethacin. Therefore, our objective was to identify other human placental ABC transporters potentially involved in limiting the trans-placental transfer of glyburide to the fetus. [(3)H]-glyburide transport was examined in brush border human placental vesicles in the presence or absence of specific inhibitors. Prepared vesicles were 70% oriented right-side-out and demonstrated 25-27 fold enrichment as compared to whole placenta. Functional studies demonstrated significant increases in the intra-vesicular accumulation of [(3)H]-glyburide in vesicles treated with the BCRP inhibitor, novobiocin. In contrast, PGP inhibition as well as MRP inhibition did not affect [(3)H]-glyburide accumulation. This is the first evidence to clearly indicate that glyburide is preferentially transported by BCRP, in the brush border of the human placenta. Our study also indicates that BCRP likely effluxes substrates in the fetal to maternal direction in the human placenta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0143-4004
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-43
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Breast cancer resistance protein: mediating the trans-placental transfer of glyburide across the human placenta.
pubmed:affiliation
University of Toronto, Department of Pharmacology, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article