Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins

Eur J Pharmacol. 2007 Apr 10;560(2-3):127-31. doi: 10.1016/j.ejphar.2007.01.051. Epub 2007 Feb 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • Animals
  • Benzbromarone / pharmacology
  • Cells, Cultured
  • Chloride Channels / antagonists & inhibitors*
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors*
  • Probenecid / pharmacology
  • Rats
  • Rats, Inbred F344
  • Sulfinpyrazone / pharmacology

Substances

  • ATP-Binding Cassette Transporters
  • Chloride Channels
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Benzbromarone
  • Probenecid
  • Sulfinpyrazone