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World J Gastroenterol. Aug 21, 2008; 14(31): 4955-4960
Published online Aug 21, 2008. doi: 10.3748/wjg.14.4955
Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro
Long-De Wang, Xiao-Qing Qiu, Zhi-Feng Tian, Ying-Fu Zhang, Hong-Fang Li
Long-De Wang, Affiliated Hospital, Gansu Chinese Medical College, Lanzhou 730020, Gansu Province, China
Xiao-Qing Qiu, Zhi-Feng Tian, Ying-Fu Zhang, Functional Lab of Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
Hong-Fang Li, Department of Physiology, College of Basic Medicine, Lanzhou University, Key Laboratory of Pre-clinical Study for New Drugs of Gansu Province, Lanzhou 730000, Gansu Province, China
Author contributions: Wang LD, Li HF designed the research; Qiu XQ, Tian ZF and Zhang YF performed the research; Wang LD and Li HF analyzed the data, wrote the paper and edited the manuscript.
Supported by The Medical Subject Fund of Lanzhou University, No. LZUYX200611, and the Post-doctoral Science Foundation of China, No. 2003034442
Correspondence to: Professor Hong-Fang Li, Department of Physiology, College of Basic Medicine, Lanzhou University, Key Laboratory of Pre-clinical Study for New Drugs of Gansu Province, 199 Donggang West Road, Lanzhou 730000, Gansu Province, China. lihf@lzu.edu.cn
Telephone: +86-931-8289576 Fax: +86-931-8912582
Received: December 24, 2007
Revised: July 26, 2008
Accepted: August 2, 2008
Published online: August 21, 2008
Abstract

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, Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from sarcoplasmic reticulum (SR), but were not related to the estrogen receptors.

Keywords: Phytoestrogen, Estradiol, Gallbladder, Smooth muscle, Ca2+ channel