Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2)

Takeshi Kawabe, Zhe Sheng Chen, Morimasa Wada, Takeshi Uchiumi, Mayumi Ono, Shin Ichi Akiyama, Michihiko Kuwano

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

We established stable human canalicular multispecific organic anion transporter (cMOAT/MRP2) cDNA transfectants, CHO/cMOAT from non-polarized Chinese hamster ovary (CHO)-K1 and LLC/cMOAT from polarized pig kidney epithelial LLC-PK1. Human cMOAT was mainly localized in the plasma membrane of CHO/cMOAT and in the apical membrane of LLC/cMOAT. The ATP-dependent uptake of leukotriene C4 (LTC4) into CHO/cMOAT membrane vesicles was enhanced compared with empty vector transfectants. K(m) values in CHO/cMOAT membrane vesicles were 0.24 μM for LTC4 and 175 μM for ATP. Drug sensitivity to vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not to etoposide. Cellular accumulation of vincristine and cisplatin in human cMOAT cDNA transfectants decreased, but not of etoposide. The uptake of LTC4 into CHO/cMOAT membrane vesicles was inhibited by exogenous administration of vincristine or cisplatin, but not that of etoposide. Moreover, this inhibition was more enhanced in the presence of glutathione. These consequences indicate that drug resistance to vincristine or cisplatin appears to be modulated by human cMOAT through transport of the agents, possibly in direct or indirect association with glutathione. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)327-331
Number of pages5
JournalFEBS Letters
Volume456
Issue number2
DOIs
Publication statusPublished - Aug 6 1999

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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