Genistein, a tyrosine kinase inhibitor, reduces Ca2+ mobilization in swine carotid media.
Genistein, a tyrosine kinase inhibitor, reduces Ca2+ mobilization in swine carotid media.
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Genistein 是一种酪氨酸激酶抑制剂，可减少猪颈动脉中 Ca2 的动员。
DOI：
10.1152/ajpcell.1995.268.6.c1425
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Murphy,RA
中科院分区：
文献类型：
--
作者：
Gould,EM;Rembold,CM;Murphy,RA
DiSalvo及其同事（Biochem. Biophys. Res. Commun. 190：968-974，1993）发现酪氨酸激酶抑制剂在恒定Ca 2+浓度下降低透化肠系膜小动脉中的力。这些数据表明，酪氨酸激酶激活可以调节完整的血管平滑肌的Ca 2+敏感性。我们通过研究酪氨酸激酶抑制剂染料木素对完整猪颈动脉中膜组织细胞内钙离子浓度（[Ca 2 +]i）、肌球蛋白调节轻链（MRLC）磷酸化和等长应力的影响来验证这一假设。用30 μ M染料木黄酮预处理减弱组胺诱导的[Ca 2 +]i增加（使用发光蛋白水母发光蛋白估计），MRLC磷酸化和应激。[Ca 2 +]i的染料木素依赖性降低定量解释了MRLC磷酸化和应激的降低。MRLC磷酸化的Ca 2+依赖性或力对MRLC磷酸化的依赖性没有可测量的变化。染料木黄酮抑制收缩独立的激活剂Ca 2+的来源。这些数据表明，酪氨酸激酶可能通过改变[Ca 2 +]i而不是调节MRLC磷酸化的Ca 2+敏感性来影响完整猪颈动脉中膜中的力发展。
DiSalvo and colleagues (Biochem. Biophys. Res. Commun. 190: 968-974, 1993) found that tyrosine kinase inhibitors reduced force at constant Ca2+ concentrations in permeabilized mesenteric arterioles. These data suggest that tyrosine kinase activation could regulate Ca2+ sensitivity in intact vascular smooth muscle. We tested this hypothesis by examining the effects of the tyrosine kinase inhibitor genistein on intracellular Ca2+ concentration ([Ca2+]i), myosin regulatory light chain (MRLC) phosphorylation, and isometric stress in intact swine carotid media tissues. Pretreatment with 30 microM genistein attenuated histamine-induced increases in [Ca2+]i (estimated using the photoprotein aequorin), MRLC phosphorylation, and stress. The genistein-dependent decrease in [Ca2+]i quantitatively accounted for the decrease in MRLC phosphorylation and stress. There was no measurable change in the Ca2+ dependence of MRLC phosphorylation or the dependence of force on MRLC phosphorylation. Genistein inhibited contractions independently of the source of activator Ca2+. These data suggest that tyrosine kinase(s) may influence force development in the intact swine carotid media by altering [Ca2+]i rather than modulating the Ca2+ sensitivity of MRLC phosphorylation.