Actions of genistein on contractile response of smooth muscle isolated from guinea pig gallbladder

BACKGROUND:Defective contractile motility of the gallbladder is an important factor for gallstone formation.Estrogen might increase the risk of gallstones and cholecystitis,and estradiol inhibits the contractile activity of isolated strips of guinea pig gallbladder.The potential risks associated with hormone replacement therapy(HRT) include symptomatic gallstones.Phytoestrogen have been used to treat menopause syndromes by replacing traditional estrogen.This experiment aimed to determine the effects of the phytoestrogen genistein on the contractile response of smooth muscle strips isolated from guinea pig gallbladder and its possible mechanism of action.METHODS:Guinea pigs were sacrificed to remove the whole gallbladder.Two or three smooth muscle strips were cut longitudinally.Each strip was suspended in a tissue chamber containing Krebs solution.After 2 hours of equilibration,contractile response indexes were recorded.Different concentrations of genistein were added to the chamber and the contractile responses were measured.Each antagonist was added 2 minutes before genistein to study possible mechanisms.The effect of genistein on calcium-dependent contraction curves and biphasic contraction in calcium-free Krebs solution were measured.RESULTS:Genistein decreased the resting tension dose-dependently,and reduced the mean contractile amplitude and frequency in gallbladder strips.Ranitidine partly inhibited the effect of genistein,but methylene blue,Nω-nitro-L-arginine,and propranolol hydrochloride did not influence this action.Genistein had no significant effects on calcium-dependent contraction.Genistein reduced the first contraction induced by acetylcholine chloride,but did not affect the second contraction caused by CaCl2.CONCLUSIONS:Genistein relaxed smooth muscle isolated from the gallbladder of guinea pigs and this might contribute to the formation of gallstones.The inhibitory action might be related to H2 receptors and the release of intracellular Ca 2+ from sarcoplasmic reticulum.Replacing traditional estrogen with phytoestrogen to treat menopause syndromes may increase the risk of gallstone formation.