Structural determinants for activation and block of CFTR-mediated chloride currents by apigenin

Beate Illek, Mike E. Lizarzaburu, Vivien Lee, Michael H. Nantz, Mark J. Kurth, Horst Fischer

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Apigenin (4',5,7-trihydroxyflavone) is an activator of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl- currents across epithelia at low concentrations and a blocker at high concentrations. We determined the roles of structural components of apigenin for both stimulation and block of Cl- currents across Calu-3 epithelia. The half-maximal binding affinity of apigenin for current stimulation (K(S)) was 9.1 ± 1.3 μM, and the rank-order of molecular structures was 7-hydroxyl > pyrone = 4'-hydroxyl > 5-hydroxyl. Both the 7-hydroxyl and the 4'-hydroxyl served as H-bond acceptors, whereas the 5-hydroxyl was an H-bond donor. The half-maximal binding affinity of apigenin during current block was 74 ± 11 μM. Blocked Cl- currents were structurally determined by 7-hydroxyl = 4'-hydroxyl > pyrone > 5-hydroxyl. Prestimulation of tissues with forskolin significantly affected activation kinetics and binding characteristics. After forskolin stimulation, K(S) was 4.1 ± 0.9 μM, which was structurally determined by pyrone > all hydroxyls > single hydroxyls. In contrast, block of Cl- current by apigenin was not affected by forskolin stimulation. We conclude that apigenin binds to a stimulatory and an inhibitory binding site, which are distinguished by their affinities and the molecular interactions during binding.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6 48-6
StatePublished - 2000


  • Binding site
  • Chloride transport
  • Cystic fibrosis transmembrane conductance regulator
  • Epithelia
  • Flavonoids
  • Resveratrol

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)


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