THE RESEARCH FOR THE ROLES OF BRADYKININ RECEPTORS IN THE INFLAMMATORY RESPONSE

缓激肽受体在炎症反应中的作用研究

基本信息

批准号：
10672155
负责人：
UENO Akinori
金额：
$ 2.05万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672155/
关键词：
BRADYKININ INFLAMMATION ANTAGONIST RECEPTORS アンタゴニスト

项目摘要

In this study, we studied the roles of the receptors of bradykinin, which was involved in the exudation and pain in the inflammatory processes. We analyzed the cDNA of bradykinin receptors, B1 and B2. We found that the B1 receptor was inducible and the B2 receptor was constitutive. And then, we investigated the mechanisms of intracellular transduction by kinin receptors, B1 and B2. It was shown that the phenomenon induced by the stimulation of B1 or B2 receptor, such as an increase of intracalcium concentration and the activation of AP-1 through the MAPK activation, were occurred, which were common. We tested the relaxization and constriction of rat ileum and duodenum by the B1 and B2 agonists. In the ileum, the response to B1 agonist was induced time- and tempatature-dependently, whereas, in the duodenum, the response to the B1 agonist was occurred from the beginning. The proteinkinase C was involved in the expression of B1 receptor, which was inhibited by pretreatment with antiinflammatory steroid, dexamethasone, After the pretreatment with endotoxin, the hypotensive response to a B1 agonist was found. In the experiment of carrageenin-induced paw edemaformation, a B1 agonist also caused the edema formation. The intense inflammatory response was induced by co-exitence of both bradykinin and prostaglandins, in which production the regulation by cytokines seemed to be important. In order to clarify the role of bradykinin on the inflammatory pain, the pain response in the paw edema models was studied. The direct evidence that bradykinin would be involved in the pain was obtained by using the kininogen-deficient rats. And also, the activation of neurotic calls by stimulation with bradykinin was found. From the above results, it was concluded that bradykinin might have the several roles in the inflammatory response, and that the inducible B1 receptor might be possibly involved in.

在这项研究中，我们研究了炎症过程中渗出和疼痛涉及的松曲蛋白受体的作用。我们分析了Bradykinin受体B1和B2的cDNA。我们发现B1受体是可诱导的，并且B2受体是组成型。然后，我们研究了Kinin受体B1和B2的细胞内转导机制。结果表明，发生了B1或B2受体刺激引起的现象，例如钙内浓度的增加和通过MAPK激活的AP-1激活，这是常见的。我们通过B1和B2激动剂测试了大鼠回肠和十二指肠的松弛和收缩。在回肠中，对B1激动剂的响应是依赖于时间和温度的，而在十二指肠中，从一开始就发生了对B1激动剂的反应。蛋白系C参与了B1受体的表达，在用内毒素进行预处理后，发现了对B1激动剂的降压反应，通过抗炎类固醇（地塞米松）抑制了B1受体的表达。在曲霉素诱导的PAW水肿的实验中，B1激动剂也引起了水肿的形成。激烈的炎症反应是由Bradyinin和Prostaglandins共存引起的，其中细胞因子调节似乎很重要。为了阐明心动激肽在炎症性疼痛中的作用，研究了PAW水肿模型中的疼痛反应。通过使用依诺原缺陷型大鼠获得疼痛的直接证据表明将与疼痛有关。而且，还发现了通过用心动激肽刺激神经质调用的激活。从以上结果得出结论，松曲素可能在炎症反应中具有多个作用，并且可能参与诱导型B1受体。