Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms

doi:10.1016/j.ejphar.2008.08.032

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	Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms
	Li, HF; Zhang, YF; Tian, ZF; Qiu, XQ; Gu, J; Wu, LX; Li, HF (reprint author), Lanzhou Univ, Coll Basic Med, Dept Physiol, 199 Donggang W Rd, Lanzhou 730000, Peoples R China.
刊名	EUROPEAN JOURNAL OF PHARMACOLOGY
	2008-11-12
卷号	597 期号:1-3 页码:70-74
关键词	Genistein Myocardial contractility Sarcoplasmic reticulum Ca2+ mobilization Cyclic adenosine 5 '-monophosphate PI3K activity
ISSN号	0014-2999
DOI	10.1016/j.ejphar.2008.08.032
文献子类	Article
英文摘要	The purpose of this study was to investigate the mechanisms involved in the excitatory effect induced by genistein in isolated guinea pig left ventricular papillary muscles and to determine relationship of genistein action with the tyrosine kinase pathway and phosphaticlylinositol 3-kinase (PI3K) activity, the cyclic adenosine 5'-monophosphate (cAMP) signal system and the sarcoplasmic reticulum Ca2+ mobilization. Genistein (1-100 mu M) significantly increased contraction of left ventricular papillary muscles from male and female guinea pigs in a concentration-dependent manner and its action had no obvious gender differences. Prior treatment with an L-type Ca2+ channel blocker verapamil hydrochloride, P-adrenoceptor inhibitors propranolol and atenolol, an inhibitor of Na+-Ca2+ reverse exchanger Kb-Gamma 7943 or the blocker of estrogen receptor ICI 182,780 failed to alter the positive inotropic effect induced by genistein in papillary muscles. However, tyrosine phosphatase inhibitor, sodium orthovanadate or a potent phosphotyrosine phosphatase inhibitor bpV (phen) could partly but significantly reduce the stimulatory action of genistein. Interestingly, insulin-like growth factor-1, a known PI3K activator could also decrease the stimulatory action of genistein obviously, but the PI3K inhibitor LY294002 had no significant effect on the stimulatory action of genistein. The excitatory effect of genistein was markedly attenuated not only after treatment with an inhibitor of cAMP synthesis Sq 22536, carbachol or an inhibitor of specific protein kinase A H-89, but also after the inhibition of sarcoplasmic reticulum Ca2+ mobilization by ruthenium red, ryanodine or the inhibitor of sarcoplasmic reticulum Ca2+-ATPase thapsigargin. All these results indicate that the excitatory effects of genistein in papillary muscles are due to the inhibition of tyrosine kinase pathway and PI3K activity, thereby locally activating cAMP signal transduction and facilitating intracellular Ca2+ mobilization, but are not related to the activation of beta-adrenoceptor, the Na+-Ca2+ reverse exchange and the estrogen receptor. (C) 2008 Elsevier B.V. All rights reserved.
学科主题	Pharmacology & Pharmacy
出版地	AMSTERDAM
资助项目	中央高校基本科研业务费专项资金
项目编号	Medical Subject Fund of Lanzhou University [LZUYX200611]
语种	英语
WOS记录号	WOS:000260920300011
资助机构	LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/121393]
专题	基础医学院_期刊论文
通讯作者	Li, HF (reprint author), Lanzhou Univ, Coll Basic Med, Dept Physiol, 199 Donggang W Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Li, HF,Zhang, YF,Tian, ZF,et al. Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2008,597(1-3):70-74.
APA	Li, HF.,Zhang, YF.,Tian, ZF.,Qiu, XQ.,Gu, J.,...&Li, HF .(2008).Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms.EUROPEAN JOURNAL OF PHARMACOLOGY,597(1-3),70-74.
MLA	Li, HF,et al."Genistein stimulates myocardial contractility in guinea pigs by different subcellular mechanisms".EUROPEAN JOURNAL OF PHARMACOLOGY 597.1-3(2008):70-74.