Differential action of a protein tyrosine kinase inhibitor, genistein, on the positive inotropic effect of endothelin‐1 and norepinephrine in canine ventricular myocardium
Differential action of a protein tyrosine kinase inhibitor, genistein, on the positive inotropic effect of endothelin‐1 and norepinephrine in canine ventricular myocardium
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DOI：
10.1038/sj.bjp.0706097
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发表时间：
2005-02
影响因子：
7.3
通讯作者：
L. Chu;Jian-xin Zhang;I. Norota;M. Endoh
中科院分区：
文献类型：
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作者：
L. Chu;Jian-xin Zhang;I. Norota;M. Endoh
1在犬离体室壁小梁和Indo-1负载的单个心肌细胞的乙酰甲酯上进行实验，以探讨蛋白酪氨酸激酶在去甲肾上腺素串扰引起的内皮素-1变力作用中的作用。金雀异黄素可抑制ET-1的正性肌力作用和低浓度与NE串扰引起的钙瞬变增加。3Genistein和大豆苷元可拮抗高浓度ET-1与NE串扰引起的负性肌力作用和钙瞬变的减少，但染料木素不影响卡巴胆碱的抗肾上腺素作用。4Genistein而不是大豆苷元通过β-肾上腺素受体增强内源性神经递质的正性肌力作用和钙瞬变的增加。金雀异黄素的增强作用可被蛋白酪氨酸磷酸酶抑制剂钒酸所阻断。5这些结果表明，金雀异黄素(1)具有正性变力作用，并伴随钙瞬变的增加，(2)抑制与去甲肾上腺素(NE)的串扰引起的ET-1的正性变力作用，(3)通过抑制β-肾上腺素能受体增强去甲肾上腺素(NE)的正性变力作用。此外，金雀异黄素通过一种与PTK无关的机制抑制ET-1对去甲肾上腺素的负性变力作用。PTK可能在受体介导的犬心室肌收缩功能调节中发挥关键作用。英国药理学杂志(2005)144,430-442。DOI：10.1038/sj.bjp.0706097
1Experiments were carried out in isolated canine ventricular trabeculae and acetoxymethylester of indo‐1‐loaded single myocytes to elucidate the role of protein tyrosine kinase (PTK) in the inotropic effect of endothelin‐1 (ET‐1) induced by crosstalk with norepinephrine (NE). The PTK inhibitor genistein was used as a pharmacological tool.2Genistein but not daidzein inhibited the positive inotropic effect and the increase in Ca2+transients induced by ET‐1 by crosstalk with NE at low concentrations.3Genistein and daidzein antagonized the negative inotropic effect and the decrease in Ca2+transients induced by ET‐1 by crosstalk with NE at high concentrations, but genistein did not affect the antiadrenergic effect of carbachol.4Genistein but not daidzein enhanced the positive inotropic effect and the increase in Ca2+transients induced by NEvia β‐adrenoceptors, while the enhancing effect of genistein was abolished by the protein tyrosine phosphatase inhibitor vanadate.5These findings indicate that genistein (1) induces a positive inotropic effect in association with an increase in Ca2+transients, (2) inhibits the positive inotropic effect of ET‐1 induced by crosstalk with NE, and (3) enhances the positive inotropic effect of NE inducedvia β‐adrenoceptors by inhibition of PTK. In addition, genistein inhibits the negative inotropic effect of ET‐1 induced by crosstalk with NE through a PTK‐unrelated mechanism. PTK may play a crucial role in the receptor‐mediated regulation of cardiac contractile function in canine ventricular myocardium.British Journal of Pharmacology(2005)144, 430–442. doi:10.1038/sj.bjp.0706097