Genistein stimulates electrogenic Cl(-) secretion in mouse jejunum

We used the short-circuit current (I(sc)) technique to investigate the effects of the isoflavone genistein on the electrogenic Cl(-) secretion of the mouse jejunum. Genistein stimulated a sustained increase in I(sc) that was dose dependent. Bumetanide inhibited 76 +/- 5% of the genistein-stimulated I(sc) consistent with activation of Cl(-) secretion. Genistein failed to stimulate I(sc) following maximal activation of the cAMP pathway by forskolin. In addition, forskolin had a reduced effect on I(sc) of the mouse jejunum in the presence of genistein. Glibenclamide, a blocker of CFTR, eliminated the genistein-stimulated increase of I(sc) and reduced the forskolin-activated I(sc). Clotrimazole, a Ca(2+)-activated K(+) channel blocker, failed to reduce the genistein-stimulated I(sc). Vanadate, a blocker of tyrosine-dependent phosphatases, reduced the genistein-activated I(sc). Tyrphostin A23, a tyrosine kinase inhibitor, reduced basal I(sc), after which genistein failed to stimulate I(sc). These data suggest that genistein activated a sustained Cl(-) secretory response of the mouse jejunum and that the effect of genistein was via a tyrosine-dependent phosphorylation pathway.