期刊
PHARMACOLOGICAL RESEARCH
卷 61, 期 1, 页码 76-84出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2009.07.002
关键词
Xenopus laevis oocyte; P-glycoprotein; Drug efflux; ABC transporter
资金
- Kobuchisawa Research Laboratories
- Fuji Biomedix Co., Ltd.
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. [H-3]Vinblastine efflux by MDR1-expressing oocytes was detectable and afforded a K-m of 145.5 +/- 25.4 mu M. [H-3]Vinblastine (5.6 +/- 0.3 mu M) and [H-3]digoxin (1.0 +/- 0.1 mu M) were individually injected into MDR1-expressing oocytes and their efflux monitored. Quinidine and verapamil, known MDR1 substrates/inhibitors, showed trans-inhibition on MDR1-mediated [H-3]vinblastine and [H-3]digoxin efflux. Conversely, doxorubicin demonstrated cis-inhibition without trans-inhibition on MDR1-mediated [H-3]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. (C) 2010 Elsevier Ltd. All rights reserved.
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