Multidrug resistance-associated protein (MRP) mediated transport of daunomycin and leukotriene C4 (LTC4) in isolated plasma membrane vesicles.
Studies have been carried out to examine in vitro drug transport in plasma membrane vesicles isolated from HL60/ADR cells that overexpress MRP. The results demonstrate that glutathione (GSH) enhances transport of daunomycin. A greater increase in transport activity occurs when the reaction is carried out in the presence of both GSH and sodium chloride. Sodium chloride alone has no effect on daunomycin transport. It has also been observed that GSH in the presence of sodium chloride induces a major increase in the transport level of LTC4. Thus far, no metal ion other than sodium chloride has been found to be active in the drug transport system. Kinetic analysis reveals that GSH in the presence of sodium chloride greatly reduces Km and increases Vmax, for daunomycin. Additional studies show that ATPase activity in isolated plasma membrane from HL60/ADR cells is greatly enhanced in the presence of both GSH and sodium chloride. These results suggest the possibility that GSH and sodium chloride stimulate MRP-mediated transport as a result of increased ATPase activity.
Ding
G Y
GY
Division of Biology, Kansas State University, Manhattan 66506, USA.
Shen
T
T
Center
M S
MS
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D005978:Glutathione / Q000494:pharmacology; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012965:Sodium Chloride / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000251:Adenosine Triphosphatases; D003630:Daunorubicin; D005978:Glutathione; D017997:Leukotriene C4; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012965:Sodium Chloride