Linked Life Data

21106720

Source:http://linkedlifedata.com/resource/pubmed/id/21106720

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-18
pubmed:abstractText
Multidrug resistance-associated protein (Mrp) 2-deficient (TR(-)) Wistar rats have been used to elucidate the role of Mrp2 in drug disposition. Decreased breast cancer resistance protein (Bcrp) levels were reported in sandwich-cultured hepatocytes (SCH) from TR(-) rats compared with those from wild-type (WT) rats. This study was designed to characterize hepatic Bcrp expression and function in TR(-) rats, using nitrofurantoin and pitavastatin as substrates. Bcrp was knocked down by RNA interference in rat SCH. Antibody BXP53, but not BXP21, specifically detected Bcrp knockdown in SCH. Bcrp protein levels were decreased markedly in TR(-) but not Mrp2-deficient Sprague-Dawley [Eisai hyperbilirubinemic rats (EHBR)] rats. Bcrp mRNA levels were decreased significantly in TR(-) livers as determined by TaqMan real-time reverse transcriptase-polymerase chain reaction. Biliary excretion of nitrofurantoin, a specific Bcrp substrate, was decreased significantly in SCH and isolated perfused livers from TR(-) rats compared with those from WT controls, indicating that hepatic Bcrp function is decreased in TR(-) rats. In Bcrp knockdown SCH, the biliary excretion index and in vitro biliary clearance of pitavastatin were decreased significantly to ? 58 and ? 52% of control, respectively, indicating that Bcrp plays a role in pitavastatin biliary excretion. Pitavastatin biliary excretion was decreased significantly in perfused livers from TR(-) compared with those from WT rats. In conclusion, expression and function of hepatic Bcrp are decreased significantly in TR(-) rats. The potential role of both Bcrp and Mrp2 should be considered when data generated in TR(-) rats are interpreted. TR(-) and EHBR rats in combination may be useful in differentiating the role of Mrp2 and Bcrp in drug/metabolite disposition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
441-7
pubmed:dateRevised
2011-6-21
pubmed:meshHeading
pubmed-meshheading:21106720-ATP-Binding Cassette Transporters, pubmed-meshheading:21106720-Animals, pubmed-meshheading:21106720-Animals, Genetically Modified, pubmed-meshheading:21106720-Anti-Bacterial Agents, pubmed-meshheading:21106720-Bile, pubmed-meshheading:21106720-Biliary Tract, pubmed-meshheading:21106720-Biological Transport, pubmed-meshheading:21106720-Cells, Cultured, pubmed-meshheading:21106720-Gene Expression Regulation, pubmed-meshheading:21106720-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:21106720-Hyperbilirubinemia, pubmed-meshheading:21106720-Liver, pubmed-meshheading:21106720-Male, pubmed-meshheading:21106720-Metabolic Clearance Rate, pubmed-meshheading:21106720-Nitrofurantoin, pubmed-meshheading:21106720-Quinolines, pubmed-meshheading:21106720-RNA, Messenger, pubmed-meshheading:21106720-RNA, Small Interfering, pubmed-meshheading:21106720-RNA Interference, pubmed-meshheading:21106720-Rats
pubmed:year
2011
pubmed:articleTitle
Decreased hepatic breast cancer resistance protein expression and function in multidrug resistance-associated protein 2-deficient (TR?) rats.
pubmed:affiliation
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural