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

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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.