Genistein activates CFTR-mediated Cl- secretion in the murine trachea and colon

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 (Isc) in tracheal (16.4 +/- 2.8 mu A/cm(2)) and colonic (40.0 +/- 4.4 mA/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 Isc of the tracheal epithelium (0.9 +/- 1.1 mu A/cm(2)) and decreased the Isc of colons from CF null (-13.1 +/- 2.3 mu A/cm(2)) and Delta F508 mice (-10.3 +/- 1.3 mu A/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 DF508 mice were also studied: 46% of trachea showed no response to genistein, whereas 54% gave an increase in Isc similar to that in wild type. We conclude that genistein activates CFTR-mediated Cl- secretion in the murine trachea and distal colon.