Inhibitory effect of quercetin on rat trachea contractility <I>in vitro</I>

Abstract

The effect of quercetin, a naturally occurring flavonoid traditionally used to treat airway diseases such as bronchial asthma, on the contractile response elicited by electrical field stimulation or carbachol in rat isolated trachea was investigated. Isolated tracheal tissue was subjected to contractions by an electrical field stimulation of 5 Hz for 30 s, 400 mA, and the responses in the presence of cumulative concentrations of quercetin (10(-6)-3x10(-4) M) were observed. The effect of quercetin was also evaluated after administration of phentolamine plus propranolol (to block alpha- and beta-adrenergic receptors), NG-nitro-L-arginine methyl ester (to block nitric oxide synthesis), capsaicin (to desensitise sensory C fibres), alpha-chymotrypsin (a proteolytic enzyme that rapidly degrades vasoactive intestinal peptide), SR140333 and SR48968 (tackykinin NK1 and NK2 receptor antagonists, respectively). Quercetin produced a concentration-dependent inhibition of contractions induced by both carbachol and electrical field stimulation. However, quercetin was more active in inhibiting the contractions produced by electrical field stimulation than those induced by carbachol, suggesting a presynaptic site of action (in addition to a postsynaptic effect, as revealed by the inhibitory action of quercetin on carbachol-induced contractions). The inhibitory effect of quercetin on contractions induced by electrical field stimulation was unaffected by phentolamine plus propranolol, SR 140333 and SR 48968, capsaicin treatment or by the proteolytic enzyme alpha-chymotrypsin. In contrast, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the inhibitory effect of quercetin on contractions induced by electrical field stimulation. Quercetin inhibits rat tracheal contractility through a presynaptic (involving nitric oxide) and a postsynaptic site of action.