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

Tullia Diena1, Raffaella Melani, Emanuela Caci

  • 1Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, and Centro di Biotecnologie Avanzate, 16148 Genoa, Italy.

European Journal of Pharmacology
|February 27, 2007
PubMed

Insights

Known multidrug resistance-associated protein inhibitors, including sulfinpyrazone, probenecid, and benzbromarone, were found to inhibit cystic fibrosis transmembrane conductance regulator (CFTR) Cl- currents by blocking the channel pore.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial Cl- channel protein.
  • CFTR shares structural similarities with multidrug resistance-associated proteins (MRPs) involved in xenobiotic transport.

Purpose of the Study:

  • To investigate whether known MRP inhibitors affect CFTR channel activity.
  • To identify potential modulators of CFTR function.

Main Methods:

  • Electrophysiological recordings of CFTR Cl- currents.
  • Application of known MRP inhibitors (sulfinpyrazone, probenecid, benzbromarone) to assess their effect on CFTR.

Main Results:

  • Sulfinpyrazone, probenecid, and benzbromarone were identified as inhibitors of CFTR.
  • These compounds block the CFTR channel pore, reducing Cl- conductance.

Conclusions:

  • Established MRP inhibitors can modulate CFTR activity.
  • This finding suggests a potential therapeutic avenue for targeting CFTR channel function using existing drug compounds.

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