Pro-inflammatory effects induced by bradykinin in a murine model of pleurisy.
Bradykinin caused a dose-related increase in cell influx 4 h after its administration into the mouse pleural cavity (ED50 = 3.2 nmol/cav., 95% confidence limits = 0.6-15.5). Cell influx peaked at 4 h and remained elevated for up to 72 h, whereas exudation was detected between 2 and 6 h after bradykinin administration. Both HOE 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]bradykinin) and NPC 17731 (D-Arg0-[Hyp3 D-HypE(transpropyl7)Oic8]bradykinin) inhibited bradykinin-induced cell influx (ID50 0.028 (0.05-0.16) and 0.4 (0.3-0.7) pmol/cav., respectively). Des-Arg9-[Leu8]bradykinin (0.1 and 3.0 nmol/cav., 30 min before) did not inhibit the effects of bradykinin. Pre-treatment of animals with either indomethacin, terfenadine, dexamethasone, N(omega)-nitro-L-arginine benzyl ester, cromolyn, theophylline, salbutamol, FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-propyl]N-met hyl-N-phenyl-methyl-3-(2-naphthyl)-L-alaninamide) or SR 142801 ((N)-(1-[3-[1-benzoyl-3-(3,4-dichloro-phenyl)-piperidin-3-yl]pr opy l]-4-phenyl-piperidin-4-yl)-N-methyl-acetamide) significantly inhibited cell migration (P < 0.01). These results indicate that bradykinin had a significant pro-inflammatory effect on the pleural cavity of the mice. This effect seems to be primarily mediated via activation bradykinin B2 receptors which trigger the release of other mediators.
Saleh
T S
TS
Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.
Calixto
J B
JB
Medeiros
Y S
YS
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002465:Cell Movement / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D009504:Neutrophils; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010994:Pleura / Q000166:cytology; D010998:Pleurisy / Q000139:chemically induced*; D043782:Receptor, Bradykinin B2; D013997:Time Factors
D001549:Benzamides; D065168:Bradykinin Receptor Antagonists; D004151:Dipeptides; D007211:Indoles; D009842:Oligopeptides; D010880:Piperidines; D043782:Receptor, Bradykinin B2; C078949:FK 888; C071327:NPC 17731; C073839:SR 48968; C065679:icatibant; D001920:Bradykinin