Cystic fibrosis genistein

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), a chloride (CF) channel characterised by chloride permeability and secretion, and also by the regulation of other epithelial ion channels (Eidelman et al, 2001). Mutations in the CFTR gene lead to an impaired or absent Cl conductance in the epithelial apical membrane, which leads to defective Cl secretion and absorption across the epithelium. Genistein (Illek et al, 1995 Weinreich et al, 1997) and other flavonoids (Illek and Fisher, 1998) have been shown, in different animal and tissue models, to activate wild-type CFTR and CFTR mutants by (Eidelman et al, 2001 Roomans, 2001 Suaud et al, 2002) ... 

Schmidt A, Hughes LK, Cai Z, Mendes F, Li H, Sheppard DN, Amaral MD. 2008. Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator. Br J Pharmacol 153 1311— 1323. 

Valero MS, Garay RP, Gros P, Alda JO. 2006. Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and Na-K-Cl cotransporter NKCC1 isoform mediate the vasorelaxant action of genistein in isolated rat aorta. Eur J Pharmacol 544 126-131. 

Extensive studies have been performed on the influence of flavonoids on the properties of the cystic fibrosis transmembrane conductance regulator (CFTR) channel. The best-known CFTR channel activator is genistein (42) [293,294], but this channel could also be activated by apigenin (23), kaempferol (28), and quercetin (29) [295], which appeared to be even more potent activators than genistein (42). CFTR channel activation by genistein (42) was not accompanied by an increase of intracellular cAMP level, which... 

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