Potent inhibition of the CFTR chloride channel by suramin

Naunyn Schmiedebergs Arch Pharmacol. 1999 Oct;360(4):473-6. doi: 10.1007/s002109900096.


After phosphorylation by protein kinase A and in the presence of ATP, the cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel. In this study we have examined the effects of suramin on the CFTR Cl- current (I(CFTR)) in excised inside-out macropatches from Xenopus oocytes expressing human CFTR; glibenclamide, the standard inhibitor of I(CFTR), and some congeners were tested in comparison. I(CFTR) was activated by addition of the catalytic subunit of protein kinase A and MgATP to the bath. Suramin inhibited I(CFTR) with an IC50 value of 1 microM and a Hill coefficient close to 1; the inhibition showed little voltage dependence and was easily reversed upon washout of the drug. In comparison, glibenclamide inhibited I(CFTR) with an IC50 value of approximately 20 microM. When tested against I(CFTR) in whole oocytes, bath application of suramin was ineffective whereas glibenclamide was about four times weaker than in the inside-out patch configuration. The data show that suramin is the most potent inhibitor of CFTR yet described and suggest that the compound approaches its site of action from the cytosol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects*
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology
  • Dose-Response Relationship, Drug
  • Glyburide / analogs & derivatives
  • Glyburide / pharmacology
  • Humans
  • Oocytes
  • Patch-Clamp Techniques
  • Phenolphthalein / pharmacology
  • Phthalic Acids / pharmacology
  • Suramin / pharmacology*
  • Time Factors
  • Xenopus laevis


  • CFTR protein, human
  • Phthalic Acids
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Suramin
  • phthalic acid
  • Phenolphthalein
  • Adenosine Triphosphate
  • Cyclic AMP-Dependent Protein Kinases
  • Glyburide