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Regulation of smooth muscle contraction through remodeling of actin filaments

通过肌动蛋白丝重塑调节平滑肌收缩

基本信息

批准号：
17500277
负责人：
WATANABE Masaru
金额：
$ 2.24万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1)Mechanism of the inhibitory effects of Phx-1 on the smooth muscle contraction To elucidate the mechanisms of relaxing effect of 2-amino-4,4 a-dihydro-4 a-7-dimethyl-3H-phenoxazine-3-one (Phx-1) on the smooth muscle preparations, we investigated effects of Phx-1 on the contraction of both intact and skinned (cell membrane peremeabilized) preparations from guinea pig tenia cecum. In intact preparations, Phx-1 concentration-dependently suppressed the contraction induced by either acetycholine(ACh) or high-K+ with the IC50 value estimated at around 100 pM. Similar inhibitory actions of Phx-1 on force were observed in intracellular Ca store depleted preparations. In the cell membrane depolarized preparations in the absence of extracellular Ca, however, Phx-1 had little effects on the caffeine-or ACh-induced contraction. In skinned preparations, Phx-1 suppressed the Ca^<2+->induced contraction at concentrations higher than 100 μM. These results suggest that Phx-1 seems to have direct inhib … More itory effect on the actin filaments organization, although inhibitory effect, of the Phx-1 on the Ca^<2+>-influx is much stronger.2)Contractile filaments remodeling by blebbistatin, a potent inhibitor of myosin II We studied the effects of blebbistatin, a potent inhibitor of myosin II on the mechanical and structural properties of beta escin skinned taenia cecum. Blebbistatin inhibited both Ca^<2+> induced contraction with only little effects on the Ca^<2+> sensitivity for the force, and 30 mM Mg^<2+> induced, myosin phosphorylation independent, force development, Also, blebbistatin accelerated relaxation by Ca^<2+> removal. IC_<50> values of the blebbistatin effects presented above were nearly 25 micro M. The present results suggested that blebbistain directly interfare cross-bridge interaction. Furthermore, blebbistatin inhibited organization of actin-and myosin-filaments. Since blebbistatin did not bind to actin directly, disruption of myosin filaments seemed to modulate actin filaments organization. Less

1)Phx-1抑制豚鼠盲肠平滑肌收缩的机制为探讨Phx-1对豚鼠盲肠肌条的舒缩作用机制，我们研究了Phx-1对豚鼠盲肠肌条完整和去皮(细胞膜透性)的收缩作用。在完整的制剂中，Phx-1呈浓度依赖性地抑制乙酰胆碱(ACh)或高K+引起的收缩，IC50值估计约为100 pm在细胞内钙储备耗竭的制剂中，Phx-1对FORCE也有类似的抑制作用。然而，在没有细胞外钙的细胞膜去极化制剂中，Phx-1对咖啡因或ACh诱导的收缩几乎没有影响。在皮肤制剂中，Phx-1在高于100μM的浓度下抑制Ca~(2+)引起的收缩。这些结果表明，Phx-1似乎直接抑制…。虽然Phx-1对肌球蛋白II的抑制作用更强，但它对肌动蛋白细丝组织的影响要强得多。2)肌球蛋白II的有效抑制剂Blebbistatin对收缩细丝重构的影响我们研究了Blebbistatin对β-七叶皂苷皮盲肠带的力学和结构特性的影响。Blebbistatin抑制Ca^&lt；2+&gt；引起的收缩，但对钙敏感性的影响很小，30 mM mg^&lt；2+&gt；诱导的肌球蛋白不依赖于磷酸化，力量的发展，同样，blblebistatin通过去除Ca^&lt；2+&gt；促进松弛。上述气泡抑素效应的IC50和GT；值接近25微米。目前的结果表明，气泡素直接作用于跨桥作用。此外，Blebbistatin抑制肌动蛋白和肌球蛋白细丝的组织。由于Blebbistatin不直接与肌动蛋白结合，肌球蛋白细丝的破坏似乎调节了肌动蛋白细丝的组织。较少