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

Abstract

1 The¯avonol quercetin has been shown to activate a Cl 7 secretion in rat colon. Unlike the secretory activity of the related iso¯avone 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. 2 In intact epithelium, quercetin induced an increase in short-circuit current (I sc ), which was diminished by the Cl 7 channel blockers NPPB and DPC, but not by glibenclamide, DIDS or anthracene-9-carboxylic acid. The e ect of the¯avonol was also inhibited by several serosally applied K + channel blockers (Ba 2+ , quinine, clotrimazole, tetrapentylammonium, 293B), whereas other K + channel blockers failed to in¯uence the quercetin-induced increase in I sc (tetraethylammonium, charybdotoxin). 3 The apical membrane was permeabilized by mucosal addition of nystatin and a serosally directed K + gradient was applied. The successful permeabilization was con®rmed by experiments demonstrating the failure of bumetanide to inhibit the carbachol-induced current. 4 In apically permeabilized epithelium, quercetin induced a K + current (I K ), which was neither in¯uenced by ouabain nor by bumetanide. Whereas DPC, NPPB, charybdotoxin and 293B failed to inhibit this I K , quinine, Ba 2+ , clotrimazole and tetrapentylammonium were e ective blockers of this current. 5 We conclude from these results that at least part of the quercetin-induced Cl 7 secretion can be explained by an activation of basolateral K + channels.

The Chemopreventive Agent Resveratrol Stimulates Cyclic AMP–Dependent Chloride SecretionIn vitro

“…Moreover, resveratrol could interact directly with CFTR as this mode of interaction could be shown for other flavonoids, e.g., genistein and quercetin. Indeed, quercetin-induced Cl À secretion was at least in part mediated by activation of basolateral K + channels in the rat distal colonic mucosa (39).…”

Basolateral Ca2+‐dependent K+‐channels play a key role in Cl—secretion induced by taurodeoxycholate from colon mucosa

“…Indeed, the prosecretory effect of quercetin persisted in the Ca 2+ -free buffer (which was not the case for TDC). It is known that Cl -secretion induced by quercetin does not require the activation of cyclic AMP-activated K + basolateral KCNQ1/KCNE3 channels (Cermak et al, 2002). Although not directly investigated in the present model, this might also apply to the prosecretory effect of TDC.…”

“…It has been shown that quercetin induces Cl -secretion via selective activation of the Ca 2+ -dependent K + basolateral rSK4 channels (Cermak et al, 2002;Devor et al, 1997). Here we show that clotrimazole, an rSK4 channel blocker (Devor et al, 1997), completely inhibited TDC-induced increase in I SC .…”

“…Within other compounds able to stimulate electrogenic transport across colon mucosa, the bioflavonoid quercetin, which is unavoidably consumed with the every-day plant food-enriched diet, added to the serosal side is able to increase I SC and Cl -secretion from the rat colonic mucosa (Cermak et al, 1998). This stimulus occurs via a Ca 2+ dependent mechanism that activates basolateral K + channels (Cermak et al, 2002).…”

Cellular Mechanism for Potentiation of Ca2+-mediated Cl– Secretion by the Flavonoid Baicalein in Intestinal Epithelia

“…The best known examples are quercetin (a flavonol) and genistein (an isoflavone). Recent studies have shown that quercetin stimulates Cl Ϫ secretion across rat colonic mucosa (11,12). This secretory activity does not depend on cAMP but depends on Ca 2ϩ , possibly via a Ca 2ϩ /calmodulin-dependent pathway.…”