Role of caveolin located in the caveolae, identified as flask-shaped invaginations on the surface of the plasma membrane, involved in the mechanotrasduction of vascular system.

小窝是细胞质膜表面的瓶状内陷，是细胞信号传递的热点，包括离子通道在内的多种功能蛋白定位在小窝中，并相互组装，从而导致生物学和药理功能的表达。1)脑动脉和肺动脉的机械转导和酪氨酸激酶/酪氨酸磷酸化：研究了压力引起的肌源性收缩与酪氨酸磷酸化有关的机制。同时测定细胞内钙离子浓度和血管内径。此外，我们试图用免疫细胞化学方法原位检测动脉中总酪氨酸磷酸化水平和pp60src的活性。2)蛋白激酶C亚型在激动性刺激和实验性脑血管痉挛增强冠状动脉收缩中的细胞内定位：Endoth…低浓度的Elin-1在10-100pM时增强5-羟色胺引起的猪冠状动脉收缩，这与蛋白激酶(PKC)a和d亚型的易位相一致。对枕大池注射自体血诱发的犬实验性脑血管痉挛模型进行了PKC亚型的研究。在血管痉挛的发展过程中，PKC d被移位到膜部分，而PKC a在已建立的血管痉挛的晚期被移位。PKC a和d亚型密集分布于富含小窝蛋白的组分中。3)讨论和未来的发展：目前的结果表明，酪氨酸激酶如src家族和PKC a和d亚型在小窝中组装，并在收缩等生物功能的表达中发挥调节作用。完善心血管系统免疫细胞化学原位检测和免疫沉淀方法。我们还将开展一项新的药理研究，旨在同时检测生物功能和原位分子动力学。较少

Caveolae, identified as flask-shaped invaginations on the surface of the plasma membrane, have been considered to be hot spots for cell signaling, A variety of functional proteins, including ion channels, are localized in caveolae, and assembled with each other, resulting in expression of biological and pharmacological functions. We summarize herewith our results as following :1) Mechanotransduction and tyrosine kinase / tyrosine phosphorylation in cerebral and pulmonary arteries :The mechanisms of pressure-induced myogenic contraction was studied with regard to tyrosine phosphrylation were studied. Intracellular Ca concentration and vessel diameter were simultaneously measured. Furthermore, we tried to detect immunocytochemically in situ total tyrosine phosphorylation level and activity of pp60src in the arteries.2) Intracellular localization of protein kinase C isoforms in the contractile potentiation of coronary artery by agonistic stimuli and experimental cerebral vasospasm :Endoth … More elin 1 at a low concentration of 10-100pM potentiated 5-hydroxytryptamine-induced contraction of porcine coronary artery, which was consistent with translocation of protein kinase (PKC) a and d isoforms. Canine model of experimental cerebral vasospasm induced by injection of autologous blood injected into cisterna magna was also investigated with regard to PKC isoforms. PKC d was translocated to the membrane fraction during the development of the vasospasm, and PKC a was tanslocated in the late phase of established vasospasm. PKC a and d isoforms were densely located in caveolin-rich fraction. Furthermore, we suggest that mechanical stress such as stretch induces activation and down-regulation of PKC a in caveolae.3) Discussion and future development :The present results suggest that tyrosine kinase such as src family and PKC a and d isoforms assembles in caveolae and play a regulatory role in the expression of biological function such as contraction. We will improve the methods of immunocytochemical in situ detection and immunoprecipitation in the cardiovascular system. We will also develop a new pharmacological study aiming to detect simultaneously biological function and molecular dynamics in situ. Less