Reminescences

https://doi.org/10.5599/admet.3.1.142

Differential effects of mitogen-activated protein kinase pathway inhibitors on P-glycoprotein activation

Hirokazu Wakuda ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan
Shino Miyauch ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan
Kana Maruyama ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan
Satomi Kagota ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan
Kazuki Nakamura ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan
Keizo Umegaki ; Information Center, National Institute of Health and Nutrition , 1 - 23 - 1 Toyama, Shinjuku - ku, Tokyo 162 - 8636, Japan
Shizuo Yamada ; Center for Pharma - Foo d Research (CPFR), Graduate School of Pharmaceutical Sciences, University of Shizuoka , 52 - 1 Yada, Suruga - ku, Shizuoka, Shizuoka 422 - 8526, Japan
Kazumasa Shinozuka ; Department of Pharmacology, School of Pha rmacy and Pharmaceutical Sciences, Mukogawa Women’s University , 11 - 68 Koshien, Kyuban - cho, Nishinomiya 663 - 8179, Japan

Abstract

The aim of this study was to evaluate the effects of the mitogen-activated protein kinase (MAPK) pathway inhibitors SB203580, CMPD-1, SB239063, SP600125, and FR180204 on the activity of P-glycoprotein (P-gp) and to assess whether the MAPK pathway affects P-gp directly. Changes in the fluorescence of residual rhodamine 123, a marker of P-gp activity, in the apical region of Caco-2 cells were measured in the presence of MAPK pathway inhibitors using time-lapse confocal laser scanning microscopy at 0, 10, 20, 30, and 60 min. Significant differences were observed between the fluorescence levels of control cells and cells treated with SB203580 for 20, 30, or 60 min. However, no significant change was observed in the residual rhodamine 123 fluorescence of cells treated with CMPD-1, SB239063, SP600125, or FR180204. Among the p38-MAPK pathway inhibitors investigated, CMPD-1 and SB239063 showed no detectable effect on the activity of P-gp. Further, JNK 1, 2, 3-MAPK pathway (SP600125) and ERK1/2 pathway (FR180204) inhibitors did not affect P-gp activity. However, SB203580 enhanced the transfer of rhodamine 123 across the apical cell membrane. Thus, SB203580 activated P-gp, although not through the p38-MAPK pathway. Importantly, the MAPK pathway did not affect P-gp activity shortly after treatment.

Keywords

Confocal laser scanning microscopy; MAPK; SB203580

Hrčak ID:

137566

URI

https://hrcak.srce.hr/137566

Publication date:

31.3.2015.

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