Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins.
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.
Diena
Tullia
T
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, and Centro di Biotecnologie Avanzate, 16148 Genoa, Italy.
Melani
Raffaella
R
Caci
Emanuela
E
Pedemonte
Nicoletta
N
Sondo
Elvira
E
Zegarra-Moran
Olga
O
Galietta
Luis J V
LJ
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
D018528:ATP-Binding Cassette Transporters; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001553:Benzbromarone; D011339:Probenecid; D013442:Sulfinpyrazone