MECHANISMS FOR THE ACTION OF VASOACTIVE SUBSTANCES AND GROWTH FACTORS.

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，我们还采用了一些受体mRNA水平的测量。主要研究结果如下：血管松弛剂的作用机制(1)我们发现异丙肾上腺素和罂粟碱不仅降低了[Ca^<2+>]i，而且降低了肌丝对Ca^<2+>的敏感性。(2)Nicorandil可降低Ca^<2+>敏感性和[Ca^<2+>]i2。(1)内皮素-1 （ET-1）和ET-3诱导的猪冠状动脉收缩存在差异。(2)乙醇诱导冠状动脉收缩的机制与g蛋白的活化有关。(3)观察去甲肾上腺素和血清素诱导兔股动脉收缩的差异。(4)研究了血管紧张素II （Ang II）和cAMP对Ang II受体mRNA表达的影响。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g蛋白诱导[Ca^<2+>]i升高。(2)胃动素可诱导血管内皮细胞Ca^<2+>瞬态。(3)确定了猪ET_A受体的序列。生长因子的研究。我们发现血小板衍生生长因子在原代培养的大鼠主动脉平滑肌细胞中没有升高[Ca^<2+>]i。气管平滑肌细胞的研究。局部麻醉利多卡因通过降低肌丝对Ca^<2+>的敏感性来放松气管平滑肌。

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.