ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells.
AUTOR(ES)
Horio, M
RESUMO
Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the "MDR1" gene, whose product is the plasma membrane P-glycoprotein. Plasma membrane vesicles partially purified from multidrug-resistant human KB carcinoma cells, but not from drug-sensitive cells, accumulate [3H]vinblastine in an ATP-dependent manner. This transport is osmotically sensitive, with an apparent Km of 38 microM for ATP and of approximately equal to 2 microM for vinblastine. The nonhydrolyzable analog adenosine 5'-[beta, gamma-imido]triphosphate does not substitute for ATP but is a competitive inhibitor of ATP for the transport process. Vanadate, an ATPase inhibitor, is a potent noncompetitive inhibitor of transport. These results indicate that hydrolysis of ATP is probably required for active transport of vinblastine. Several other drugs to which multidrug-resistant cell lines are resistant inhibit transport, with relative potencies as follows: vincristine greater than actinomycin D greater than daunomycin greater than colchicine = puromycin. Verapamil and quinidine, which reverse the multidrug-resistance phenotype, are good inhibitors of the transport process. These results confirm that multidrug-resistant cells express an energy-dependent plasma membrane transporter for hydrophobic drugs, and establish a system for the detailed biochemical analysis of this transport process.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=280257Documentos Relacionados
- Proton motive force-driven and ATP-dependent drug extrusion systems in multidrug-resistant Lactococcus lactis.
- Characterization of an ATP-dependent DNA strand transferase from human cells.
- Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells.
- Comparison of ion channels in multidrug-resistant and -sensitive human leukemic cells.
- ATP-dependent transport of organic anions in secretory vesicles of Saccharomyces cerevisiae.