title: Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein that belongs to the same family as multidrug resistance-associated proteins whose main function is to expel xenobiotics and physiological organic anions from the cell interior. Despite the overall structural similarity with these membrane proteins, CFTR is not an active transporter but is instead a Cl- channel. We have tested the ability of known inhibitors of multidrug resistance-associated proteins to affect CFTR Cl- currents. We have found that sulfinpyrazone, probenecid, and benzbromarone are also inhibitors of CFTR activity, with a mechanism involving blockage of the channel pore.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, and Centro di Biotecnologie Avanzate, 16148 Genoa, Italy.
authors.forename: Tullia
authors.initials: T
authors.lastname: Diena
authors.forename: Raffaella
authors.initials: R
authors.lastname: Melani
authors.forename: Emanuela
authors.initials: E
authors.lastname: Caci
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pedemonte
authors.forename: Elvira
authors.initials: E
authors.lastname: Sondo
authors.forename: Olga
authors.initials: O
authors.lastname: Zegarra-Moran
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000818:Animals; D001553:Benzbromarone / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors*; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013442:Sulfinpyrazone / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001553:Benzbromarone; D011339:Probenecid; D013442:Sulfinpyrazone