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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-2-3
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pubmed:abstractText |
P-glycoprotein (P-gp; MDR1) recognizes and actively transports many structurally diverse compounds (hydrophobic neutral and cationic). We studied MDR1-mediated drug transport using a high-throughput (96-well) oocyte expression system. MDR1-expressing oocytes contained sufficient ATP levels to conduct fundamental efflux studies; the optimal experimental temperature was 25 degrees C. [(3)H]Vinblastine efflux by MDR1-expressing oocytes was detectable and afforded a K(m) of 145.5+/-25.4microM. [(3)H]Vinblastine (5.6+/-0.3microM) and [(3)H]digoxin (1.0+/-0.1microM) were individually injected into MDR1-expressing oocytes and their efflux monitored. Quinidine and verapamil, known MDR1 substrates/inhibitors, showed trans-inhibition on MDR1-mediated [(3)H]vinblastine and [(3)H]digoxin efflux. Conversely, doxorubicin demonstrated cis-inhibition without trans-inhibition on MDR1-mediated [(3)H]vinblastine efflux. The MDR1-expressing oocyte system offers researchers with an alternative in vitro method to screen compounds and may allow one to probe P-gp drug-drug and/or drug-inhibitor interactions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1096-1186
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2009 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
76-84
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pubmed:meshHeading |
pubmed-meshheading:19631272-Adenosine Triphosphate,
pubmed-meshheading:19631272-Animals,
pubmed-meshheading:19631272-Biological Transport, Active,
pubmed-meshheading:19631272-Digoxin,
pubmed-meshheading:19631272-Dose-Response Relationship, Drug,
pubmed-meshheading:19631272-Doxorubicin,
pubmed-meshheading:19631272-Drug Interactions,
pubmed-meshheading:19631272-Female,
pubmed-meshheading:19631272-High-Throughput Screening Assays,
pubmed-meshheading:19631272-Humans,
pubmed-meshheading:19631272-Kinetics,
pubmed-meshheading:19631272-Microinjections,
pubmed-meshheading:19631272-Oocytes,
pubmed-meshheading:19631272-P-Glycoprotein,
pubmed-meshheading:19631272-Quinidine,
pubmed-meshheading:19631272-Temperature,
pubmed-meshheading:19631272-Verapamil,
pubmed-meshheading:19631272-Vinblastine,
pubmed-meshheading:19631272-Xenopus laevis
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pubmed:year |
2010
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pubmed:articleTitle |
Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux.
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pubmed:affiliation |
Kobuchisawa Research Laboratories, Fuji Biomedix Co., Ltd., Hokuto-shi, Yamanashi, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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