Modulation of kinin B1 but not B2 receptors-mediated rat paw edema by IL-1beta and TNFalpha.
The modulatory effects of IL-1beta and TNF alpha on the rat paw edema induced by B1 agonists have been analyzed. In naive rats, i.d. injection of B1 agonists, des-Arg9-bradykinin and des-Arg10-kallidin (up to 300 nmol), causes a minimal increase in paw volume, while the B2 agonist tyrosine8-bradykinin (0.3-10 nmol) induces graded paw edema. The injection of des-Arg9-bradykinin (10-100) nmol or des-Arg10-kallidin (1-100 nmol), in paws pre-treated with IL-1beta or TNF alpha (both 5 ng/paw; 60 and 30 min prior, respectively), caused a graded edema formation. The edemas induced by des-Arg9-bradykinin (100 nmol) were evident at 15 min, reaching the maximum 60 and 30 min after treatment with IL-1beta (0.64 +/- 0.06 ml) or TNF alpha (0.47 +/- 0.05 ml), respectively, being reduced at 360 min. The B1 antagonist des-Arg9-NPC 17731 (1-30 nmol), but not the B2 antagonist Hoe 140 (10 nmol), produced marked inhibition of des-Arg9-bradykinin-induced paw edema. Dexamethasone (0.5 mg/kg, s.c., 4 h) or cycloheximide (1.5 mg/kg, s.c., 6 h) significantly prevented the edema caused by des-Arg9-bradykinin (100 nmol) in rats treated with IL-1beta (81 +/- 5% and 59 +/- 3%) or TNF alpha (78 +/- 4% and 43 +/- 2%). Indomethacin (2 mg/kg, i.p.) or meloxicam (3 mg/kg, i.p.), 1 h prior, significantly reduced the edema induced by des-Arg9-bradykinin (100 nmol) in IL-1beta (40 +/- 6% and 69 +/- 8%) or TNF alpha (43 +/- 3% and 53 +/- 9%) treated rats. It is suggested that i.d. injection of the IL-1beta or TNF alpha, produced up-regulation of B1 receptor-mediated paw edema, being this effect sensitive to dexamethasone and cycloheximide and to cyclo-oxygenase pathway.
Campos
M M
MM
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Souza
G E
GE
Calixto
J B
JB
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003513:Cycloheximide / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000378:metabolism*; D006614:Hindlimb; D007267:Injections; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003513:Cycloheximide; D001920:Bradykinin