Gould E M, Rembold C M, Murphy R A
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville 22908, USA.
Am J Physiol. 1995 Jun;268(6 Pt 1):C1425-9. doi: 10.1152/ajpcell.1995.268.6.C1425.
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.
迪萨尔沃及其同事（《生物化学与生物物理研究通讯》190: 968 - 974, 1993）发现，酪氨酸激酶抑制剂在通透的肠系膜小动脉中，于恒定钙离子浓度下可降低张力。这些数据表明，酪氨酸激酶激活可能调节完整血管平滑肌中的钙离子敏感性。我们通过研究酪氨酸激酶抑制剂染料木黄酮对完整猪颈动脉中层组织细胞内钙离子浓度（[Ca2 +]i）、肌球蛋白调节轻链（MRLC）磷酸化及等长张力的影响，来验证这一假说。用30微摩尔染料木黄酮预处理可减弱组胺诱导的[Ca2 +]i升高（使用光蛋白水母发光蛋白估算）、MRLC磷酸化及张力增加。染料木黄酮依赖的[Ca2 +]i降低在数量上解释了MRLC磷酸化及张力的降低。MRLC磷酸化的钙离子依赖性或张力对MRLC磷酸化的依赖性均无明显变化。染料木黄酮抑制收缩，且与激活剂钙离子的来源无关。这些数据表明，酪氨酸激酶可能通过改变[Ca2 +]i而非调节MRLC磷酸化的钙离子敏感性，来影响完整猪颈动脉中层的张力发展。
