Gastric relaxation induced by apigenin and quercetin: analysis of the mechanism of action.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo, Viale delle Scienze, Palermo, Italy.
Alessandra
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Rotondo
Rosa
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Serio
Flavia
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Mulè
D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*
D002121:Calcium Channel Blockers; D018721:Muscarinic Agonists; D011189:Potassium Chloride; D047310:Apigenin; D002217:Carbachol; D011794:Quercetin; D000242:Cyclic AMP; D006152:Cyclic GMP; D009543:Nifedipine; D002118:Calcium