The flavonol quercetin activates basolateral K + channels in rat distal colon epithelium

The flavonol quercetin has been shown to activate a Cl − secretion in rat colon. Unlike the secretory activity of the related isoflavone genistein, quercetin's secretory activity does not depend on cyclic AMP; instead, it depends on Ca 2+ . We investigated the possible involvement of Ca 2+ dependent basolateral K + channels using apically permeabilized rat distal colon epithelium mounted in Ussing chambers. In intact epithelium, quercetin induced an increase in short‐circuit current ( I sc ), which was diminished by the Cl − channel blockers NPPB and DPC, but not by glibenclamide, DIDS or anthracene‐9‐carboxylic acid. The effect of the flavonol was also inhibited by several serosally applied K + channel blockers (Ba 2+ , quinine, clotrimazole, tetrapentylammonium, 293B), whereas other K + channel blockers failed to influence the quercetin‐induced increase in I sc (tetraethylammonium, charybdotoxin). The apical membrane was permeabilized by mucosal addition of nystatin and a serosally directed K + gradient was applied. The successful permeabilization was confirmed by experiments demonstrating the failure of bumetanide to inhibit the carbachol‐induced current. In apically permeabilized epithelium, quercetin induced a K + current ( I K ), which was neither influenced by ouabain nor by bumetanide. Whereas DPC, NPPB, charybdotoxin and 293B failed to inhibit this I K , quinine, Ba 2+ , clotrimazole and tetrapentylammonium were effective blockers of this current. We conclude from these results that at least part of the quercetin‐induced Cl − secretion can be explained by an activation of basolateral K + channels.British Journal of Pharmacology (2002) 135 , 1183–1190; doi: 10.1038/sj.bjp.0704564