title: Chlorpromazine transport in membrane vesicles from multidrug resistant CCRF-CEM cells.
abstract: The mechanism by which chlorpromazine (2-chloro-10-(3-dimethylaminopropyl)-phenothiazine) reverses P-glycoprotein (P-gp2) mediated multidrug resistance was investigated using membrane vesicles prepared from human CCRF-CEM leukaemia cells. Chlorpromazine was transported in an ATP-dependent manner into membrane vesicles prepared from vinblastine resistant (VBL1000) cells but not from drug-sensitive cells. The chlorpromazine uptake was sensitive to osmotic pressure, indicating true transport into the vesicle lumen. The ATP-dependent chlorpromazine uptake was inhibited about 30% by the addition of ammonium chloride, indicating that a pH or electrical gradient could not account for the majority of ATP-dependent chlorpromazine uptake. The results of this study show that chlorpromazine is actively transported my P-glycoprotein and that chemosensitization by phenothiazines may occur by competition of these agents for active transport of anticancer agents by P-glycoprotein.
authors.affiliation: Department of Pharmacy, University of Sydney, NSW, Australia.
authors.forename: S K
authors.initials: SK
authors.lastname: Syed
authors.forename: R I
authors.initials: RI
authors.lastname: Christopherson
authors.forename: B D
authors.initials: BD
authors.lastname: Roufogalis
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000932:Antiemetics / Q000378:metabolism*; D001693:Biological Transport, Active; D002746:Chlorpromazine / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000932:Antiemetics; D000643:Ammonium Chloride; D000255:Adenosine Triphosphate; D002746:Chlorpromazine