Expression of B1 kinin receptors mediating paw edema and formalin-induced nociception. Modulation by glucocorticoids.
Bradykinin (BK) and Tyr8-BK induced graded rat paw edema with EC50 values of 1.9 and 1.1 nmol/paw, while des-Arg9-BK (DABK, up to 300 nmol/paw) was marginally effective. Tyr8-BK, but not DABK, also caused a dose-related increase in mouse paw edema, with an EC50 of 1.3 nmol/paw. The response to Tyr8-BK (10 nmol/paw) in rat paw edema was antagonized by B2 receptor antagonists (HOE-140 or NPC 17731, 30 nmol/paw) but not by the B1 antagonist des-Arg9[Leu8]BK (DALBK, 100 nmol/paw). Daily intraplantar injections of Tyr8-BK (10 nmol/paw) for 7 days caused progressive desensitization (D) of edema in sham-operated and adrenalectomized Wistar rats. DABK (100 nmol/paw) caused marked paw edema in D paws from both groups, which was inhibited by DALBK (100 nmol/paw) and by dexamethasone (0.5mg/kg, s.c.). Systemic injection of lipopolysaccharide (10 micrograms/mouse, 24 h prior) potentiated the first and second phases of Formalin-induced pain but had no effect on paw edema. Coinjection of DABK (2-22 nmol/paw) with low doses of Formalin in lipopolysaccharide-treated mice, which had no effect on naive animals, dose dependently potentiated both phases of Formalin-induced pain but did not modify paw edema. These effects were antagonized by DALBK with ID50 values of 21.9 (first phase) and 64.1 (second phase) nmol/paw. Thus, both progressive desensitization of B2 receptors and systemic treatment with lipopolysaccharide induce a glucocorticoid-sensitive upregulation of B1 receptors mediating paw edema in the rat and Formalin-induced nociception in mice. These results suggest that induction of upregulation of B1 receptors may play important roles in controlling inflammatory processes and hyperalgesia.
Campos
M M
MM
Department of Pharmacology, Universidade Federal de Santa Catarina, Brazil.
Mata
L V
LV
Calixto
J B
JB
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000209:etiology*; D005557:Formaldehyde; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D010146:Pain / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*
D065168:Bradykinin Receptor Antagonists; D008070:Lipopolysaccharides; D018002:Receptors, Bradykinin; D005557:Formaldehyde; D003907:Dexamethasone