The secretory response of the rat colon to the flavonol quercetin is dependent on Ca2+-calmodulin

Abstract

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 (Isc), 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 Ca2+ release from intracellular stores (TMB-8), whereas the muscarinic receptor antagonist atropine was ineffective. The quercetin-induced Isc was abolished in Ca2+-free solution. The flavonol was able to further increase Isc after maximal stimulation of the cAMP pathway by forskolin. The Isc 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 Isc increase induced by forskolin. These results indicate that the chloride secretion induced by quercetin in rat colon depends on Ca2+ and calmodulin. The cAMP pathway and inhibition of phosphodiesterase appear not to be responsible for the secretory activity of the flavonol.

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

“…This secretory activity does not depend on cAMP but depends on Ca 2ϩ , possibly via a Ca 2ϩ /calmodulin-dependent pathway. The cAMP pathway and inhibition of phosphodiesterase appear not to be responsible for the secretory activity of the flavonol (13). On the other hand, genistein can activate both wild type and mutant cystic fibrosis transmembrane conductance regulator (CFTR), 1 probably through direct binding of the channel (14).…”