Aims
Recently, flavonoids have been shown to cause murine gastric relaxation. In the present study we examined the mechanism of action underlying gastric relaxation induced by apigenin and quercetin in isolated mouse stomach. Main
Methods
The mechanical activity from the whole stomach was detected as changes in the endoluminal pressure and the response to increasing concentrations of both flavonoids were tested before and after different pharmacological treatments. Key findings: Apigenin and quercetin-induced a concentration-dependent gastric relaxation, apigenin being more potent than quercetin. The responses were unaffected by 2'5'dideoxyadenosine, an inhibitor of adenylate cyclase, 3-isobutyl-1-methylxanthine, a non selective inhibitor of cyclic nucleotide phosphodiesterase, or ryanodine, an inhibitor of calcium release from ryanodine-sensitive intracellular stores, whereas they were significantly decreased in Ca(2+)-free solution or in the presence of nifedipine, a blocker of L-type voltage-dependent Ca(2+) channels, which did not modify the relaxation induced by isoproterenol. Moreover, both flavonoids caused concentration-dependent inhibition of the contractile responses caused by exogenous application of Ca(2+) in a Ca(2+)-free solution, high K(+) or carbachol. Significance: Our
Significance
Our results support the hypothesis that the gastric myorelaxant effects of apigenin and quercetin arise from their negative modulation of calcium influx through voltage-dependent Ca(2+) channels, however intracellular modulation of signalling cascade leading to contraction could be involved.