title: Modulation of MRP1-like efflux activity in human erythrocytes caused by membrane perturbing agents.
abstract: The effect of membrane perturbing agents on the efflux (37 degrees C, 60 min) of the fluorescent probe 2', 7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes was studied. Several anionic amphiphiles (detergents) markedly inhibited BCPCF efflux (IC50 < or = 40 microM). Most zwitter-ionic amphiphiles were inefficient inhibitors. Non-ionic and cationic amphiphiles had minor effects or increased efflux. Of the aliphatic inhibitors, C12-homologues were the most efficient. Hexanol, ethanol, methyl-beta-cyclodextrin (MbetaCD) and diamide (+ washing) did not influence BCPCF efflux. It is suggested that amphiphiles affect BCPCF efflux by modulating multi-drug resistance protein 1 (MRP1, ABCC1) activity. A negative charge of amphiphiles is essential for the inhibitory effect, while alkyl chain length modulates inhibition. MRP1-mediated BCPCF efflux appears to be relatively insensitive to non-specific plasma membrane modification.
authors.affiliation: Department of Biology, Abo Akademi University, FIN-20520 Abo/Turku, Finland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bobrowska-Hägerstrand
authors.forename: Anna
authors.initials: A
authors.lastname: Wróbel
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mrówczyńska
authors.forename: Thomas
authors.initials: T
authors.lastname: Söderström
authors.forename: Henry
authors.initials: H
authors.lastname: Hägerstrand
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D003902:Detergents / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects*
chemical_list: D003902:Detergents; D005452:Fluoresceins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C473073:2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein