Direct effects of 9-anthracene compounds on cystic fibrosis transmembrane conductance regulator gating

Pflugers Arch. 2004 Oct;449(1):88-95. doi: 10.1007/s00424-004-1317-y.


Anthracene-9-carboxylic acid (9-AC) has been reported to show both potentiation and inhibitory effects on guinea-pig cardiac cAMP-activated chloride channels via two different binding sites, and inhibition of Mg(2+)-sensitive protein phosphatases has been proposed for the mechanism of 9-AC potentiation effect. In this study, we examined the effects of 9-AC on wild-type and mutant human cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels expressed in NIH3T3 or CHO cells. 9-AC inhibits whole-cell CFTR current in a voltage-dependent manner, whereas the potentiation effect is not affected by membrane potentials. Anthracene-9-methanol, an electro-neutral 9-AC analog, fails to block CFTR, but shows a nearly identical potentiation effect, corroborating the idea that two chemically distinct sites are responsible, respectively, for potentiation and inhibitory actions of 9-AC. 9-AC also enhances the activity of deltaR-CFTR, a constitutively active CFTR mutant whose R-domain is removed. In excised inside-out patches, 9-AC increases Po by prolonging the mean burst durations and shortening the interburst durations. We therefore conclude that two different 9-AC binding sites for potentiation and inhibitory effects on CFTR channels are located outside of the R-domain. We also speculate that 9-AC potentiates CFTR activity by directly affecting CFTR gating.

Publication types

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

MeSH terms

  • Animals
  • Anthracenes / metabolism*
  • Anthracenes / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Guinea Pigs
  • Humans
  • Ion Channel Gating / drug effects*
  • Mice
  • NIH 3T3 Cells
  • Patch-Clamp Techniques


  • Anthracenes
  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 9-anthroic acid