MECHANISMS FOR THE ACTION OF VASOACTIVE SUBSTANCES AND GROWTH FACTORS.

血管活性物质和生长因子的作用机制。

• 批准号: 05837016
• 负责人: NISHIMURA Junji
• 金额: $ 1.09万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05837016/
• 关键词: Vascular Smooth Muscle; Calcium Ion; Muscle Contraction; Cell Proliferation; Molecular Biology

In the present study, the mechanisms for the action of vasoactive substances and growth factors were investigated, using simultaneous measurements of intracellular calcium concentration ([Ca^<2+>]i) and tension of the various vascular tissues and vascular endothelial cells. To further explore the mechanisms, we also employed the measurements of mRNA level of some kind of receptors. The major findings were as follows.1.Mechanisms for the vasorelaxants(1)We found the isoproterenol and papavrine decreases not only [Ca^<2+>]i but also Ca^<2+> sensitivity of the myofilaments.(2)Nicorandil was found to decrease Ca^<2+> sensitivity as well as [Ca^<2+>]i2.Mechanisms for the contraction induced by agonists(1)The endothelin-1 (ET-1) and ET-3 induced contraction of the porcine coronary artery were found to be different.(2)The mechanisms for the ethanol-induced contraction of the coronary artery were found to involve the activation of G-protein.(3)The difference of the norepinephrine-and serotonin-induced contraction of the rabbit femoral artery were investigated.(4)The effects of angiotensin II (Ang II) and cAMP on the expression of Ang II receptor mRNA were investigated.3.Investigation of the vascular endothelial cells(1)We found that ET-1 induced the increase in [Ca^<2+>]i partially through pertussis toxin sensitive G-protein.(2)Motilin was found to induce Ca^<2+> transients of the vascular endothelial cells.(3)The sequence of the pig ET_A receptor were determined.4.Investigation of the growth factor.We found that platelet derived growth factor progresses the cell cycle without the rise in [Ca^<2+>]i of the rat aortic smooth muscle cells in primary culture.5.Investigation of the tracheal smooth muscle cells.Lidocaine, a local anesthesia, was found to relax tracheal smooth muscle by reducing the Ca^<2+> sensitivity of the myofilaments.

在本研究中，通过同时测量细胞内钙浓度([Ca^2+]i)和各种血管组织和血管内皮细胞的张力，研究了血管活性物质和生长因子的作用机制。为了进一步探讨其机制，我们还测量了某种受体的 mRNA 水平。主要研究结果如下：1.血管舒张剂的作用机制(1)我们发现异丙肾上腺素和罂粟碱不仅降低肌丝的[Ca^<2+>]i，而且降低肌丝的Ca^<2+>敏感性。(2)尼可地尔被发现降低Ca^<2+>敏感性以及[Ca^<2+>]i2。 (1)发现内皮素1(ET-1)和ET-3引起的猪冠状动脉收缩存在差异。(2)发现乙醇引起的冠状动脉收缩机制涉及G蛋白的激活。(3)去甲肾上腺素和5-羟色胺引起的兔股动脉收缩的差异 (4)研究血管紧张素II(Ang II)和cAMP对Ang II受体mRNA表达的影响。3.血管内皮细胞的研究(1)我们发现ET-1部分通过百日咳毒素敏感的G蛋白诱导[Ca^<2+>]i增加。(2)胃动素可诱导血管内皮细胞Ca^<2+>瞬变。 (3)测定猪ET_A受体的序列。4.生长因子的研究。我们发现血小板源性生长因子促进细胞周期进展，而原代培养的大鼠主动脉平滑肌细胞的[Ca^2+]i不增加。5.气管平滑肌细胞的研究。利多卡因是局麻药，通过减少气管平滑肌的 肌丝的Ca^2+敏感性。

项目成果

Miyagi Y: "The resting load-regulated sensitivity of vascular smooth muscle is mediated by a [Ca^<2+>]i-insensitivity mechanism." Am J Physiol. (in press).

Miyagi Y：“血管平滑肌的静息负荷调节敏感性是由 [Ca^2>]i 不敏感性机制介导的。”

Miyagi,Y.: "Resting load regulates cytosolic calcium-force relationship of the contraction of bovine cerebrovascular smooth muscle." J.Physiol.(in press).

Miyagi,Y.：“静息负荷调节牛脑血管平滑肌收缩的胞质钙力关系。”

Higuchi Y: "Motilin induces the endothelium-dependent relaxation of smooth muscle and the elevation of cytosolic calcium in endothelial cells in situ." Biochem Biophys Res Commun. 202. 346-353 (1994)

Higuchi Y：“胃动素诱导平滑肌的内皮依赖性松弛和原位内皮细胞中胞质钙的升高。”

Toyofuku K: "Effects of U46619 on intracellular Ca^<2+> concentration and tension in human umbilical artery." Am.J.Gynecol.Obstetrics. (in press).

Toyofuku K：“U46619 对人脐动脉细胞内 Ca^2 浓度和张力的影响。”

Ushio-Fukai,M.: "Effets of isoprenaline on cytosolic calcium concentrations and on tension in the porcine coronary artery." J.Physiol.462. 679-696 (1993)

Ushio-Fukai，M.：“异丙肾上腺素对胞质钙浓度和猪冠状动脉张力的影响。”