The flavonol quercetin activates basolateral K(+) channels in rat distal colon epithelium.
1. 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. 2. 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). 3. 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. 4. 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. 5. 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.
Cermak
Rainer
R
Institut für Veterinär-Physiologie, Universität Zürich, Winterthurerstrasse 260, 8057 Zürich, Switzerland. cermak@aninut.uni-kiel.de
Kuhn
Gisela
G
Wolffram
Siegfried
S
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D049994:Sodium Potassium Chloride Symporter Inhibitors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011794:Quercetin; D000254:Sodium-Potassium-Exchanging ATPase