Reversal effects of Ca2+ antagonists on multidrug resistance via down-regulation of MDR1 mRNA

Chiho Komoto; Tsutomu Nakamura; Motohiro Yamamori; Nobuko Ohmoto; Hironao Kobayashi; Akiko Kuwahara; Kohshi Nishiguchi; Kohji Takara; Yusuke Tanigawara; Noboru Okamura; Katsuhiko Okumura; Toshiyuki Sakaeda

Reversal effects of Ca²⁺ antagonists on multidrug resistance via down-regulation of MDR1 mRNA

Chiho Komoto, Tsutomu Nakamura, Motohiro Yamamori, Nobuko Ohmoto, Hironao Kobayashi, Akiko Kuwahara, Kohshi Nishiguchi, Kohji Takara, Yusuke Tanigawara, Noboru Okamura, Katsuhiko Okumura, Toshiyuki Sakaeda

Department of Pharmacokinetics and Pharmacodynamics

Research output: Contribution to journal › Article

8 Citations (Scopus)

Abstract

In previous reports, the effects of 12 Ca²⁺ antagonists on a multidrug resistant transporter, P-glycoprotein/MDR1, were evaluated in terms of those on MDR1-mediated transport of [³H]digoxin and the sensitivity of vinblastine sulfate or paclitaxel, and they were able to be classified into 4 subgroups based on their actions, as those with transport inhibition and sensitivity recovery, those with or without transport inhibition but marginal sensitivity recovery, and those without both. In this study, our previous findings were confirmed by the resistance against doxorubicin hydrochloride and daunorubicin hydrochloride, and by the recovery of [³H] vinblastine sulfate accumulation. Furthermore, it was found that the effects of 12 Ca ²⁺ antagonists on the sensitivity recovery were also explained by the down-regulation of MDR1 mRNA, suggesting a novel mechanism to reverse the MDR1-mediated multidrug resistance.

Original language	English
Pages (from-to)	355-363
Number of pages	9
Journal	Kobe Journal of Medical Sciences
Volume	53
Issue number	6
Publication status	Published - 2007

Keywords

Down-regulation
MDR1/P-glycoprotein
Multidrug resistance
mRNA expression

ASJC Scopus subject areas

Medicine(all)

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Komoto, C., Nakamura, T., Yamamori, M., Ohmoto, N., Kobayashi, H., Kuwahara, A., Nishiguchi, K., Takara, K., Tanigawara, Y., Okamura, N., Okumura, K., & Sakaeda, T. (2007). Reversal effects of Ca²⁺ antagonists on multidrug resistance via down-regulation of MDR1 mRNA. Kobe Journal of Medical Sciences, 53(6), 355-363.

Reversal effects of Ca²⁺ antagonists on multidrug resistance via down-regulation of MDR1 mRNA. / Komoto, Chiho; Nakamura, Tsutomu; Yamamori, Motohiro; Ohmoto, Nobuko; Kobayashi, Hironao; Kuwahara, Akiko; Nishiguchi, Kohshi; Takara, Kohji; Tanigawara, Yusuke; Okamura, Noboru; Okumura, Katsuhiko; Sakaeda, Toshiyuki.

In: Kobe Journal of Medical Sciences, Vol. 53, No. 6, 2007, p. 355-363.

Research output: Contribution to journal › Article

Komoto, Chiho ; Nakamura, Tsutomu ; Yamamori, Motohiro ; Ohmoto, Nobuko ; Kobayashi, Hironao ; Kuwahara, Akiko ; Nishiguchi, Kohshi ; Takara, Kohji ; Tanigawara, Yusuke ; Okamura, Noboru ; Okumura, Katsuhiko ; Sakaeda, Toshiyuki. / Reversal effects of Ca²⁺ antagonists on multidrug resistance via down-regulation of MDR1 mRNA. In: Kobe Journal of Medical Sciences. 2007 ; Vol. 53, No. 6. pp. 355-363.

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