Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro

AIM： To observe and compare the effects of phytoestrogen genistein, resveratrol and 17β-estradiol on the tonic contraction and the phasic contraction of isolated gallbladder muscle strips and to study the underlying mechanisms. METHODS： Isolated strips of gallbladder muscle from guinea pigs were suspended in organ baths containing Kreb＇s solution, and the contractilities of strips were measured before and after incubation with genistein, resveratrol and 17β-estradiol respectively. RESULTS： Similar to 17β-estradiol, genistein and resveratrol could dose-dependently inhibit the phasic contractile activities, they decreased the mean contractile amplitude and the contractile frequencies of gallbladder muscle strips, and also produced a marked reduction in resting tone. The blocker of estrogen receptor ICI 182780 failed to alter the inhibitory effects induced by genistein and resveratrol, but potassium bisperoxo （1, 10 phenanthroline） oxovanadate bpV （phen）, a potent protein tyrosine phosphatase inhibitor, markedly attenuated the inhibitory effects induced by genistein and resveratrol. In calcium-free Kreb＇s solution containing 0.01 mmol/L egtazic acid （EGTA）, genistein and resveratrol inhibited the first phasic contraction induced by acetylcholine （ACh）, but did not affect the second contraction induced by CaCl2. In addition, genistein, resveratrol and 17β-estradiol also could reduce the contractile responses of ACh and KCl, and shift their cumulative concentration-response curves rightward. CONCLUSION： Phytoestrogen genistein and resveratrol can directly inhibit the contractile activity of isolated gallbladder muscle both at rest and in response to stimulation. The mechanisms responsible for the inhibitory effects probably due mainly to inhibition of tyrosine kinase, Ca^2＋ influx through potential-dependent calcium channels （PDCs） and Ca^2＋ release from sarcoplasmic reticulum （SR）, but were not related to the estrogen receptors.