کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2536911 | 1559172 | 2006 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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 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](/preview/png/2536911.png)
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 μM, 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 μM and 42 ± 11 μM 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 μM and 1.6 ± 0.5 μM, 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.
Journal: European Journal of Pharmacology - Volume 544, Issues 1–3, 21 August 2006, Pages 126–131