EXPRESSION OF B-1 KININ RECEPTORS MEDIATING PAW EDEMA AND FORMALIN-INDUCED NOCICEPTION - MODULATION BY GLUCOCORTICOIDS

Bradykinin (BK) and Tyr(8)-BK induced graded rat paw edema with EC(50) values of 1.9 and 1.1 nmol/paw, while des-Arg(9)-BK (DABK, up to 300 nmol/paw) was marginally effective. Tyr(8)-BK, but not DABK, also caus ed a dose-related increase in mouse paw edema, with an EC(50) of 1.3 n mol/paw. The response to Tyr(8)-BK (10 nmol/paw) in rat paw edema was antagonized by B-2 receptor antagonists (HOE-140 or NPC 17731, 30 nmol /paw) but not by the B-1 antagonist des-Arg(9)[Leu(8)]BK (DALBK, 100 n mol/paw). Daily intraplantar injections of Tyr(8)-BK (10 nmol/paw) for 7 days caused progressive desensitization (D) of edema in sham-operat ed and adrenalectomized Wistar rats. DABK (100 nmol/paw) caused marked paw edema in D paws from both groups, which was inhibited by DALBK (1 00 nmol/paw) and by dexamethasone (0.5 mg/kg, s.c.). Systemic injectio n of lipopolysaccharide (10 mu g/mouse, 24 h prior) potentiated the fi rst and second phases of Formalin-induced pain but had no effect on pa w edema. Coinjection of DABK (2-22 nmol/paw) with low doses of Formali n in lipopolysaccharide-treated mice, which had no effect on naive ani mals, dose dependently potentiated both phases of Formalin-induced pai n but did not modify paw edema. These effects were antagonized by DALB K with ID, values of 21.9 (first phase) and 64.1 (second phase) nmol/p aw. Thus, both progressive desensitization of B-2 receptors and system ic treatment with lipopolysaccharide induce a glucocorticoid-sensitive upregulation of B, receptors mediating paw edema in the rat and Forma lin-induced nociception in mice. These results suggest that induction of upregulation of B-1 receptors may play important roles in controlli ng inflammatory processes and hyperalgesia.