The short-chain fatty acids acetate, propionate and butyrate induced a concentration-dependent increase of short-circuit current (Isc) in the rat distal small intestine in vitro. They were ineffective in the proximal small intestine. The increase of lsc in the distal small intestine was dependent on the presence of Cl- and HCO3- ions. It was blocked by the inhibitor of the Na(+)-K(+)-Cl(-) -cotransporter, bumetanide, and by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate, indicating that short-chain fatty acids evoke an anion secretion. The secretion induced by propionate was blocked by the neurotoxin, tetrodotoxin, and inhibited by the muscarinic antagonists, atropine. In contrast, indomethacin, a cyclooxygenase inhibitor, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, were ineffective. These results indicate that short-chain fatty acids stimulate chemosensitive neurones in the rat small intestine in a region-specific manner, which induce anion secretion by the release of mainly acetylcholine.

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.

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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.