Genistein stimulates electrogenic Cl−secretion in mouse jejunum

Abstract

We used the short-circuit current ( Isc) technique to investigate the effects of the isoflavone genistein on the electrogenic Cl−secretion of the mouse jejunum. Genistein stimulated a sustained increase in Iscthat was dose dependent. Bumetanide inhibited 76 ± 5% of the genistein-stimulated Iscconsistent with activation of Cl−secretion. Genistein failed to stimulate Iscfollowing maximal activation of the cAMP pathway by forskolin. In addition, forskolin had a reduced effect on Iscof the mouse jejunum in the presence of genistein. Glibenclamide, a blocker of CFTR, eliminated the genistein-stimulated increase of Iscand reduced the forskolin-activated Isc. Clotrimazole, a Ca2+-activated K+channel blocker, failed to reduce the genistein-stimulated Isc. Vanadate, a blocker of tyrosine-dependent phosphatases, reduced the genistein-activated Isc. Tyrphostin A23, a tyrosine kinase inhibitor, reduced basal Isc, after which genistein failed to stimulate Isc. 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.