Quercetin relaxes guinea pig gallbladder strips

Quercetin, a phytoestrogen and flavonoid, relaxes intestinal and vascular smooth muscle. The purpose of this study was to determine if quercetin had an effect on gallbladder smooth muscle. An in vitro technique was used to determine the effects of quercetin on gallbladder strips and which system(s) mediated the relaxation. Paired t tests were used; differences between means of P < .05 were considered significant. Adding quercetin before cholecystokinin or KCl produced a significant (P < .001) decrease in the amount of tension (0.80 ± 0.04 vs 0.48 ± 0.04 g cholecystokinin octapeptide and 0.8 ± 0.06 vs 0.54 ± 0.05 g KCl, respectively). When the protein kinase C (PKC) inhibitors bisindolymaleimide IV and chelerythrine Cl− were simultaneously, a significant (P < .001) reduction in the quercetin-induced relaxation (45.7% ± 4.3% vs 27.6% ± 3.4%) was observed. To determine if protein kinase A (PKA) mediated the quercetin-induced relaxation, PKA inhibitor 14-22 amide myristolated was used. It significantly (P < .05) decreased the amount (40.4% ± 3.7% vs 34.5% ± 3.3%) of quercetin-induced relaxation. The use of 2-APB also significantly (P < .001) reduced the amount of quercetin-induced relaxation (51.2% ± 3.5% vs 14.8% ± 3.6%). l-NG-methyl-l-arginine acetate salt, a nitric oxide synthase inhibitor, significantly (P < 001) decreased the quercetin-induced relaxation (45.7% ± 4.2% vs 35.2% ± 3.6%). KT5823, a PKC inhibitor, had no effect on the quercetin-induced relaxation. Quercetin blocked extracellular Ca2+ entry which affected downstream events such as activation of PKC, PKA, intracellular Ca2+ release, and activation of nitric oxide synthase. Quercetin relaxed cholecystokinin octapeptide and KCl-induced tension in a concentration dependent manner. Thus quercetin-induced relaxation was mediated by multiple signaling pathways.