Journal
PHARMACOLOGY
Volume 70, Issue 1, Pages 5-14Publisher
KARGER
DOI: 10.1159/000074237
Keywords
flavonoids; quercetin; naringenin; apigenin; genistein; intestinal peristalsis; enteric nervous system; distension sensitivity; motor performance
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Flavonoids are known to relax precontracted intestinal smooth muscle and to delay intestinal transit. We therefore investigated the effects of quercetin, naringenin, apigenin and genistein on intestinal peristalsis in vitro. Peristalsis in fluid-perfused segments of the guinea pig small intestine was recorded through the intraluminal pressure changes associated with the peristaltic waves. Alterations of distension sensitivity were reflected by changes in the peristaltic pressure threshold and alterations of peristaltic performance by changes in the maximal acceleration, amplitude and residual baseline pressure of the peristaltic waves. Quercetin, naringenin, apigenin and genistein (10-300 mumol/l) depressed intestinal peristalsis in a structure- and concentration-dependent manner. The flavonoid-evoked changes in peristalsis parameters made it possible to distinguish between two patterns of peristaltic motor inhibition: a decrease in distension sensitivity and peristaltic performance (apigenin and genistein) and a decrease in distension sensitivity without a major change in peristaltic performance (quercetin and naringenin). The antiperistaltic effect of quercetin was partially prevented by apamin (0.5 mumol/l), N-nitro-L-arginine methylester (100 mumol/l) and naloxone (0.5 mumol/l), whereas the effect of genistein was hardly affected by these drugs. Peristaltic motor activity suppressed by quercetin (300 mumol/l), but not genistein (100 mumol/l), was partially restored by apamin. In contrast, neostigmine (0.3 mumol/l) caused a significant recovery of peristalsis from blockade by genistein but failed to reverse peristaltic motor blockade due to quercetin. These observations suggest that naringenin and quercetin inhibit peristalsis by facilitating inhibitory enteric pathways, whereas apigenin and genistein interfere with muscle excitation or excitation-contraction coupling. Copyright (C) 2004 S. Karger AG, Basel.
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