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The flavonol quercetin activates basolateral K + channels in rat distal colon epithelium
Author(s) -
Cermak Rainer,
Kuhn Gisela,
Wolffram Siegfried
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704564
Subject(s) - charybdotoxin , bumetanide , tetraethylammonium , dids , apamin , channel blocker , chemistry , apical membrane , epithelial polarity , quercetin , ussing chamber , glibenclamide , carbachol , transepithelial potential difference , ion transporter , potassium channel , endocrinology , paracellular transport , potassium channel blocker , medicine , membrane potential , biochemistry , biology , secretion , receptor , potassium , membrane , antioxidant , organic chemistry , diabetes mellitus , permeability (electromagnetism) , calcium
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