کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5830485 | 1559039 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genistein stimulates duodenal HCO3â secretion through PI3K pathway in mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Genistein has been proposed as a promising pharmacotherapeutic for cystic fibrosis. We recently found that genistein stimulates murine duodenal HCO3â secretion through cystic fibrosis transmembrane conductance regulator (CFTR). The aim of the present study was to determine the intracellular signal pathways involved in genistein-stimulated duodenal HCO3â secretion. Murine duodenal mucosal HCO3â secretion was examined in vitro in Ussing chambers by the pH-stat technique. The results showed that neither cAMP-dependent signal pathway inhibitors MDL-12330A and KT-5720, nor cGMP signal pathway inhibitors NS2028 and KT5823, nor calcium signal pathway inhibitors verapamil and W-13, altered genistein-stimulated duodenal HCO3â secretion. In calcium-free solution, genistein-stimulated duodenal HCO3â secretion was not altered either. Vanadate, an inhibitor of protein tyrosine phosphatase, only partially inhibited genistein-stimulated duodenal HCO3â secretion. However, both wortmannin and LY294002, two structurally and mechanistically distinct phosphatidylinositol 3-kinase (PI3K) inhibitors, markedly inhibited genistein-stimulated duodenal HCO3â secretion. Genistein increased duodenal mucosal PI3K activity and induced the phosphorylation of Akt, a signaling molecule downstream of PI3K, which was again inhibited by wortmannin. Estrogen receptor antagonist, ICI182,780, also markedly inhibited genistein-stimulated duodenal HCO3â secretion and genistein-induced PI3K activity increase in duodenal mucosa. These results demonstrate that genistein stimulates duodenal HCO3â secretion mainly through estrogen receptor and PI3K-dependent pathway. These findings contribute to the understanding of the molecular mechanism of genistein-induced anion secretion and further pharmacotherapeutic development and use of genistein or related substances in the treatment of diseases of epithelial tissues.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 651, Issues 1â3, 25 January 2011, Pages 159-167
Journal: European Journal of Pharmacology - Volume 651, Issues 1â3, 25 January 2011, Pages 159-167
نویسندگان
Biguang Tuo, Guorong Wen, Penghong Song, Jingyu Xu, Xuemei Liu, Ursula Seidler, Hui Dong,