MECHANISMS FOR THE ACTION OF VASOACTIVE SUBSTANCES AND GROWTH FACTORS.

在本研究中，血管活性物质和生长因子的作用机制进行了研究，使用细胞内钙浓度（[Ca^<2+>]i）和各种血管组织和血管内皮细胞的张力的同时测量。为了进一步探讨其作用机制，我们还对某些受体的mRNA水平进行了测定。主要结果如下：1.血管舒张药的作用机制：（1）异丙肾上腺素和罂粟碱不仅能降低肌丝[Ca^<2+>]i，而且能降低肌丝的Ca^<2+>敏感性。（2）尼可地尔可降低Ca^2+敏感性和[Ca^2+] i 2。激动剂引起的收缩作用机制：（1）内皮素-1（ET-1）和ET-3引起的猪冠状动脉收缩作用不同。（2）乙醇引起冠状动脉收缩的机制与G蛋白的激活有关。（3）比较去甲肾上腺素和长春新碱对兔股动脉收缩作用的差异。（4）血管紧张素Ⅱ（Angiotensin Ⅱ，Ang Ⅱ）和cAMP对血管内皮细胞Ang Ⅱ受体mRNA表达的影响。3.血管内皮细胞的研究（1）ET-1部分通过百日咳毒素敏感性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+>瞬变。（3）测定了猪ET_A受体的序列;（4）生长因子的研究：在原代培养的大鼠主动脉平滑肌细胞中，发现血小板衍生生长因子促进细胞周期，而不引起[Ca^<2+>]i的升高;（5）气管平滑肌细胞的研究：利多卡因局部麻醉，通过降低肌丝对Ca^2+的敏感性来松弛气管平滑肌。

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.