PMID: 9188796May 22, 1997Paper

Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion transport

Biochimica Et Biophysica Acta
M HeijnJ Lankelma

Abstract

We studied the ATP-dependent uptake of dinitrophenyl-glutathione (GS-DNP) into plasma membrane vesicles derived from parental GLC4 cells and from multidrug resistant GLC4/ADR cells. The latter have a high expression of the multidrug resistance protein (MRP). Uptake of GS-DNP into membrane vesicles from GLC4/ADR cells was highly stimulated by the addition of ATP, compared to the uptake into membrane vesicles from GLC4 cells. This ATP-dependent uptake into membrane vesicles from GLC4/ADR cells was saturable with a Km of 1.2 +/- 0.2 microM and a Vmax of 560 +/- 80 pmol/mg prot./min. ATP stimulated GS-DNP uptake with a Km of 187 +/- 4 microM. This uptake was specifically inhibited by a polyclonal serum raised against a fusion protein containing a segment of MRP. The ATP-dependent uptake of GS-DNP was not only inhibited by organic anions, such as oxidized glutathione (GSSG), methotrexate (MTX) and some bile acids, but also by non-anionic natural product drugs, such as anthracyclines, vinca alkaloids and etoposide (VP-16). Uptake of GSSG and MTX into membrane vesicles from GLC4/ADR cells could be stimulated by ATP. The ATP-dependent uptake of GSSG had a Km of 43 +/- 3 microM and a Vmax of 900 +/- 200 nmol/mg protein/min. The ATP-depe...Continue Reading

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Citations

Mar 3, 2007·Cancer Metastasis Reviews·Yehuda G Assaraf
Oct 30, 1998·Critical Reviews in Oncology/hematology·M ClynesK Scanlon
Dec 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sungpil ChoWilliam T Beck
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Dec 20, 2003·Pharmacogenomics·Toshihisa IshikawaYasuhiro Sumino
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Aug 8, 2008·Phytotherapy Research : PTR·Xiu-Wei YangWei Xu
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Nov 10, 2006·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yehuda G Assaraf
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