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

在本研究中，我们研究了缓激肽受体的作用，缓激肽参与炎症过程中的渗出和疼痛。我们分析了缓激肽受体B1和B2的cDNA。我们发现B1受体是可诱导的，B2受体是组成型的。然后，我们研究了激肽受体B1和B2在细胞内转导的机制。结果表明，在B1或B2受体的刺激下，会出现钙内浓度升高、通过MAPK激活AP-1等现象，这些现象是普遍存在的。我们观察了B1和B2激动剂对大鼠回肠和十二指肠的松弛和收缩作用。在回肠，对B1激动剂的反应是时间和温度依赖性的，而在十二指肠，对B1激动剂的反应从一开始就发生了。蛋白激酶C参与B1受体的表达，抗炎类固醇地塞米松预处理可抑制B1受体的表达，内毒素预处理后B1受体激动剂有降压作用。在角叉菜胶致足跖水肿实验中，一种B1激动剂也引起足跖水肿的形成。缓激肽和前列腺素的共存诱导了强烈的炎症反应，其中细胞因子的产生调节似乎很重要。为了阐明缓激肽在炎性疼痛中的作用，我们研究了足跖水肿模型的疼痛反应。通过使用激肽原缺乏的大鼠获得了缓激肽参与疼痛的直接证据。同时，还发现了缓激素刺激下的神经性呼叫的激活。综上所述，缓激肽在炎症反应中可能具有多种作用，诱导型B1受体可能参与其中。

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.