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, Nomega-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 Ca2+ from sarcoplasmic reticulum. Replacing traditional estrogen with phytoestrogen to treat menopause syndromes may increase the risk of gallstone formation.
Luo
Ya-Li
YL
Department of Pathology, Department of Basic Medicine, Gansu College of Tradition Chinese Medicine, Lanzhou 730000, China. mailoflyl@126.com
Wang
Ya-Li
YL
Li
Neng-Lian
NL
Zheng
Tian-Zhen
TZ
Zhang
Li
L
She
Ya-Li
YL
Hu
Shu-Ming
SM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism; D042882:Gallstones / Q000139:chemically induced; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D048789:Phytoestrogens; D011970:Receptors, Histamine H2; D019833:Genistein; D002118:Calcium