Bradykinin B1 and B2 receptors, tumour necrosis factor alpha and inflammatory hyperalgesia.
The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+ a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude.
Poole
S
S
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Lorenzetti
B B
BB
Cunha
J M
JM
Cunha
F Q
FQ
Ferreira
S H
SH
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002351:Carrageenan / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D016209:Interleukin-8 / Q000494:pharmacology; D007609:Kallidin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D012756:Sheep; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D016209:Interleukin-8; D008070:Lipopolysaccharides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D001262:Atenolol; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D002351:Carrageenan; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin