Premium
The Secretory Response of the Rat Colon to the Flavonol Quercetin is Dependent on Ca 2+ ‐Calmodulin
Author(s) -
Cermak R.,
Vujicic Z.,
Kuhn G.,
Wolffram S.
Publication year - 2000
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2000.01923.x
Subject(s) - ibmx , forskolin , calmodulin , quercetin , endocrinology , trifluoperazine , chemistry , medicine , phosphodiesterase , hexamethonium , phosphodiesterase inhibitor , ruthenium red , carbachol , stimulation , pharmacology , biochemistry , biology , calcium , enzyme , antioxidant
The dietary flavonol quercetin induces chloride secretion in rat intestine. To clarify the underlying mechanisms, experiments were performed in Ussing chambers with tissue from rat proximal and distal colon. Quercetin induced an increase in short‐circuit current ( I sc ), which was largely independent of submucosal neurons, as it was not affected by the neurotoxin tetrodotoxin. The effect of quercetin was blocked by the calmodulin antagonists trifluoperazine and ophiobolin A and was diminished by a blocker of Ca 2+ release from intracellular stores (TMB‐8), whereas the muscarinic receptor antagonist atropine was ineffective. The quercetin‐induced I sc was abolished in Ca 2+ ‐free solution. The flavonol was able to further increase I sc after maximal stimulation of the cAMP pathway by forskolin. The I sc increase by the flavonol was differently affected by two analogous phosphodiesterase inhibitors. Whereas 3‐isobutyl‐1‐methylxanthine (IBMX) antagonized the effect of quercetin, 8‐methoxymethyl‐IBMX had no effect. Both phosphodiesterase inhibitors similarly influenced the I sc increase induced by forskolin. These results indicate that the chloride secretion induced by quercetin in rat colon depends on Ca 2+ and calmodulin. The cAMP pathway and inhibition of phosphodiesterase appear not to be responsible for the secretory activity of the flavonol.