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.
Department of Physiology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Michael J
MJ
Baker
Kirk L
KL
Hamilton
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D022142:Secretory Vesicles / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014638:Vanadates; D019833:Genistein; C102635:1-ethyl-2-benzimidazolinone