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Drug transport studies by human MDR1 in Xenopus laevis oocyte expression system
Author(s) -
Jutabha Promsuk,
Narikawa Shinichi,
XiuLin Yi,
Ohtsu Naoko,
Otomo Jun,
Kadota Toshihito,
Endou Hitoshi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.633
Subject(s) - efflux , p glycoprotein , xenopus , oocyte , vinblastine , transporter , atp binding cassette transporter , multiple drug resistance , microbiology and biotechnology , chemistry , multidrug resistance associated protein 2 , drug , pharmacology , biology , biochemistry , embryo , chemotherapy , gene , genetics , antibiotics
MDR1 or P‐glycoprotein is a plasma membrane protein of mammalian cells that confers multidrug resistance by acting as ATP‐dependent efflux transporter of diverse hydrophobic neutral or cationic compounds including several important drugs used in cancer chemotherapy. Up to date MDR1‐mediated drug transport studies were performed using membrane vesicle or proteoliposome, which are not real cell systems, and also in culture cells that have limitation for drug entering to the cells at the basolateral side. We have studied MDR1‐mediated drug transport using an alternative high‐throughput oocyte expression system, OOCYTEXPRESS. This system could reduce the problem in route of drug entering to the cells by direct injection of test compounds into oocytes. The vinblastine sulfate efflux by MDR1‐expressed oocytes showed clearly significant difference from control oocytes. The efflux was increased with time and the percentage of vinblastine sulfate efflux was saturate at 30 min. Using oocyte expression system, we could demonstrate the substrates of this transporter and examine the side of inhibition of compounds for each substrate. Therefore, OOCYTEXPRESS is a useful real cell system for drug export studies. (This research was supported by Fuji Biomedix Co., Ltd.)