Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4&...

Full description

Saved in:
Bibliographic Details
Published inSheng li hsüeh pao Vol. 67; no. 2; p. 225
Main Authors Cao, Huan-Huan, Fang, Fang, Yu, Bo, Luan, Jian, Jiang, Yu, Yang, Hong
Format Journal Article
LanguageChinese
Published China 25.04.2015
Subjects
Animals
Colforsin
Colon - metabolism
Cystic Fibrosis Transmembrane Conductance Regulator - drug effects
Flavones - physiology
Flavonoids - pharmacology
Genistein
Intestinal Mucosa - metabolism
Mice
Rats
Online AccessGet more information

Cover

More Information
Summary:Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed
ISSN:0371-0874