The regulatory mechanism of smooth muscle contraction by protein kinases.

蛋白激酶对平滑肌收缩的调节机制。

• 批准号: 02454100
• 负责人: KARAKI Hideaki
• 金额: $ 4.1万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454100/
• 关键词: Smooth muscle; Contractile elements; Ca^<2+> sensitivity; Phosphorylation; Protein kinase C; Phorbol ester; 細胞内カルシウム; カルシウム感受性; ミオシンリン酸化

It is generally accepted that smooth muscle contraction is regulated by Ca^<2+>-dependent phosphorylation of myosin light chain and subsequent interaction with actin. Recently, several reports suggested that some actin binding proteins, such as caldesmon and calponin, change the actin-myosin interaction in vitro. At present, however, it is unclear if such mechanisms are involved in the contraction of intact smooth muscle. In this study, we defined several novel findings by analyzing the effects of several types of agonists on cytosolic Ca^<2+> concentration, myosin phosphorylation and contractility of intact and skinned muscles.SummaryI. In vascular and tracheal smooth muscles, the following mechanisms seemed to be involved in the contraction ;i)Ca^<2+>-dependent myosin phosphorylationii)Increase in Ca^<2+> sensitivity of myosin phosphorylationiii)Ca^<2+> -dependent and myosin phosphorylation-independent mechanismII. The mechanisms of contraction, as mentioned above, are due to an active actin/myosin interaction.III. Actin regulated mechanisms may be involved in the above mechanisms. Since the effects of phorbol esters mimic the agonists-induced contraction, activation of protein kinase C may be involved in the above mechanisms, although further experiments are necessary to clarify the role of protein kinase C.

人们普遍认为平滑肌收缩是通过肌球蛋白轻链的Ca 2+ 依赖性磷酸化以及随后与肌动蛋白的相互作用来调节的。最近，一些报告表明一些肌动蛋白结合蛋白，例如钙结合蛋白和钙调蛋白，在体外改变了肌动蛋白-肌球蛋白的相互作用。然而，目前尚不清楚这种机制是否参与完整平滑肌的收缩。在这项研究中，我们通过分析几种类型的激动剂对胞浆Ca^2+浓度、肌球蛋白磷酸化以及完整和带皮肌肉的收缩性的影响，定义了一些新的发现。在血管和气管平滑肌中，以下机制似乎与收缩有关；i)Ca^2+依赖性肌球蛋白磷酸化ii)肌球蛋白磷酸化的Ca^2+敏感性增加iii)Ca^2+依赖性和肌球蛋白磷酸化独立机制II。如上所述，收缩机制是由于活跃的肌动蛋白/肌球蛋白相互作用所致。上述机制可能涉及肌动蛋白调节机制。由于佛波酯的作用模拟激动剂诱导的收缩，因此蛋白激酶 C 的激活可能参与上述机制，尽管需要进一步的实验来阐明蛋白激酶 C 的作用。

项目成果

Kohama K, Hiramura T, Takano-Ohmuro H, Ozaki H, Karaki H, Hachisu M: "Effects of NA0344, a new smooth muscle relaxant, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in vitro." General Pharmacology. 22. 465-474 (1991)

Kohama K、Hiramura T、Takano-Ohmuro H、Ozaki H、Karaki H、Hachisu M：“NA0344（一种新型平滑肌松弛剂）对体外肌动蛋白-肌球蛋白-ATP 相互作用和肌球蛋白轻链磷酸化的影响。”

H. Ozaki,T. Ohyama,K. Sato and H. Karaki.: "Ca^<2+>-dependent and independent mechanisms of sustained contraction in vascular smooth muscle of rat aorta." Japan J. Pharmacol.52. 509-512 (1990)

H.尾崎，T.

Ishihara H,Karaki H: "Inhibitory effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate(TMB-8)in vascular smooth muscle." Europian Journal of Pharmacology. 197. 181-186 (1991)

Ishihara H、Karaki H：“8-(N,N-二乙氨基)辛基-3,4,5-三甲氧基苯甲酸酯(TMB-8)对血管平滑肌的抑制作用。”

Hori M,Magae J,Han YG,Hartshorne DJ,Karaki H: "A novel protein phosphatase inhibitor,tautomycin Effect on smooth muscle." FEBS Letters. 285. 145-148 (1991)

Hori M，Magae J，Han YG，Hartshorne DJ，Karaki H：“一种新型蛋白磷酸酶抑制剂，互变霉素对平滑肌的作用。”

H.Karaki(Ed.)Sperelakis and Kuriyama: "Ca^<2+>‐regulation of vascular smooth msucle and release of endothelium‐derived relaxing factor.In:Ion channels of vascular smooth muscle cells and endothelial cells." Elsevier Science Publishing company (NewYork.),

H.Karaki（编辑）Sperelakis 和 Kuriyama：“血管平滑肌的 Ca^2+ 调节和内皮衍生舒张因子的释放。见：血管平滑肌细胞和内皮细胞的离子通道”。公司（纽约），