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Valero, MS, Garay, RP, Gros, P and 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. 544:126-31


The soy phytoestrogen genistein is a potent vasorelaxant, but its mechanism of action is poorly understood. Here, we used endothelium-denuded rat aorta to investigate the role of the cyclic AMP(cAMP)-activated, cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, and its associated Na-K-Cl cotransporter NKCC1. Isolated, endothelium-denuded rat aorta was contracted with phenylephrine 1 microM, and the vasorelaxant responses to genistein were investigated under conditions where CFTR was inhibited by DPC (diphenylamine-2-carboxylic acid) or glibenclamide (n=6 for compound). Both compounds fully antagonized the vasorelaxant responses to genistein, with IC50=57+/-18 microM and 42+/-11 microM for DPC and glibenclamide respectively. H-89, a selective protein kinase A (PKA) inhibitor, blocked the vasorelaxant responses to genistein. Finally, the NKCC1 inhibitor, bumetanide fully antagonized the vasorelaxant responses to genistein against phenylephrine- or KCl-induced contractions, with IC50=2.0+/-0.2 microM and 1.6+/-0.5 microM, respectively (n=6 for condition). These results strongly suggest that CFTR opening is involved in the vasorelaxant action of genistein, and that cAMP-dependent CFTR phosphorylation and chloride entry via the NKCC1 cotransporter are required for genistein action.


PubMed Online version:10.1016/j.ejphar.2006.06.048


Animals; Anthranilic Acids/pharmacology; Aorta/metabolism; Aspartic Acid/metabolism; Chlorides/chemistry; Chlorides/metabolism; Cyclic AMP/metabolism; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism; Cystic Fibrosis Transmembrane Conductance Regulator/physiology; Dose-Response Relationship, Drug; Genistein/pharmacology; Inhibitory Concentration 50; Male; Nitrates/metabolism; Rats; Rats, Wistar; Sodium-Potassium-Chloride Symporters/chemistry



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status



GO:0042311: vasodilation

ECO:0000315: mutant phenotype evidence used in manual assertion


Seeded From UniProt


See also


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