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Pflügers Archiv

, Volume 434, Issue 4, pp 484–491 | Cite as

Direct action of genistein on CFTR

  • Frank Weinreich
  • Phillip G. Wood
  • John R. Riordan
  • G. Nagel
ORIGINAL ARTICLE

Abstract

 Human cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels were expressed in oocytes from Xenopus laevis after injection of CFTR cRNA and studied with the two-electrode voltage-clamp and the giant patch techniques. The tyrosine kinase inhibitor genistein alone activated a small chloride current in whole oocytes expressing CFTR and substantially increased the chloride current obtained upon stimulation with forskolin and isobutyl methylxanthine (IBMX). In giant excised patches, genistein was unable to open protein-kinase-A-phosphorylated CFTR channels in the absence of ATP, but increased the ATP-induced CFTR channel currents by a factor of 3.8 ± 1.7. This genistein-mediated potentiation in excised patches is independent of protein phosphatase activity, as it is readily reversible, even after complete inhibition of protein kinase A activity. Involvement of protein tyrosine kinases also seems unlikely, because this effect of genistein is not antagonized by high concentrations of the tyrosine phosphatase inhibitor ortho-vanadate. We, therefore, propose a direct interaction of genistein with CFTR, probably at a nucleotide binding site, which leads to a higher open probability.

Key words CFTR Chloride channel Genistein Protein kinases Xenopus laevis 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Frank Weinreich
    • 1
  • Phillip G. Wood
    • 1
  • John R. Riordan
    • 2
  • G. Nagel
    • 1
  1. 1.Max-Planck-Institut für Biophysik, D-60596 Frankfurt/M, GermanyDE
  2. 2.S. C. Johnson Medical Research Center, Mayo Clinic, Scottsdale, AZ 85259, USAUS

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