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Publication : Genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and colon.

First Author  Goddard CA Year  2000
Journal  Am J Physiol Cell Physiol Volume  279
Issue  2 Pages  C383-92
PubMed ID  10913005 Mgi Jnum  J:63991
Mgi Id  MGI:1888576 Doi  10.1152/ajpcell.2000.279.2.C383
Citation  Goddard CA, et al. (2000) Genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and colon. Am J Physiol Cell Physiol 279(2):C383-92
abstractText  The action of the isoflavone genistein on the cystic fibrosis transmembrane conductance regulator (CFTR) has been studied in many cell systems but not in intact murine tissues. We have investigated the action of genistein on murine tissues from normal and cystic fibrosis (CF) mice. Genistein increased the short-circuit current (I(sc)) in tracheal (16.4 +/- 2.8 microA/cm(2)) and colonic (40.0 +/- 4.4 microA/cm(2)) epithelia of wild-type mice. This increase was inhibited by furosemide, diphenylamine-2-carboxylate, and glibenclamide, but not by DIDS. In contrast, genistein produced no significant change in the I(sc) of the tracheal epithelium (0.9 +/- 1.1 microA/cm(2)) and decreased the I(sc) of colons from CF null (-13.1 +/- 2.3 microA/cm(2)) and DeltaF508 mice (-10.3 +/- 1.3 microA/cm(2)). Delivery of a human CFTR cDNA-liposome complex to the airways of CF null mice restored the genistein response in the tracheas to wild-type levels. Tracheas from DeltaF508 mice were also studied: 46% of trachea showed no response to genistein, whereas 54% gave an increase in I(sc) similar to that in wild type. We conclude that genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and distal colon.
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