Influence of Drugs and Nutrients on Transporter Gene Expression Levels in Caco-2 and LS180 Intestinal Epithelial Cell Lines

Pharmaceutical Research - Tập 20 Số 8 - Trang 1119-1124 - 2003
Li, Qing1, Sai, Yoshimichi1,2, Kato, Yukio1,2, Tamai, Ikumi3,2, Tsuji, Akira1,2
1Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan
2CREST (Core Research for Evolution Science and Technology) of Japan Science and Technology Corporation (JST), Japan
3Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda, Japan

Tóm tắt

Purpose. The aim of this study was to investigate the influences of various drugs and nutrients on the expression levels of intestinal drug transporters PEPT1, MDR1, MRP2 and MRP3, and drug-metabolizing enzyme CYP3A4. Methods. Quantitative reverse transcriptase polymerase chain reaction was used to quantitate transporter and CYP3A4 mRNAs. Western blotting was used to determine protein levels of P-gp. Transport studies of P-gp were performed using cultured Caco-2 cell monolayers. Results. The expression of MDR1 mRNA was increased by all-trans retinoic acid and in glucose-depleted medium, whereas little change of MRP2 and MRP3 mRNA was observed in Caco-2 cells. Substrates and inducers of P-gp or CYP3A4 tended to produce parallel changes in the expression of MDR1 and CYP3A4 mRNA in LS180 cells, whereas in Caco-2 cells no such coordinate response was observed, possibly due to the absence of the expression of steroid xenobiotic receptor (SXR) in this cell line. Conclusion. Several drugs and nutrients were found to affect transporter gene expression level in two human intestinal epithelial cell lines. Since SXR is involved in some expression-regulatory processes, and Caco-2 cells lack SXR, LS180 cells as well as Caco-2 cells should be used for the study of the regulation of intestinal transporters.

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Pharmaceutical Research

Tập 20 Số 8

1119-1124

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