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Pro-inflammatory effects induced by bradykinin in a murine model of pleurisy
T S Saleh1, J B Calixto, Y S Medeiros
1Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil.
Abstract:
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.
Insights
Bradykinin triggers significant cell influx and exudation in mouse pleural cavities, indicating a pro-inflammatory role. This effect is mediated by bradykinin B2 receptors and can be inhibited by specific antagonists and various anti-inflammatory agents.
Area of Science:
- Immunology and Inflammation Research
- Pharmacology of Inflammatory Mediators
Background:
- Bradykinin is a peptide implicated in inflammatory processes.
- Its specific role and mechanisms in pleural cavity inflammation require elucidation.
Purpose of the Study:
- To investigate the pro-inflammatory effects of bradykinin in the mouse pleural cavity.
- To identify the receptors and mediators involved in bradykinin-induced inflammation.
Main Methods:
- Administration of bradykinin into the mouse pleural cavity to assess cell influx and exudation.
- Use of bradykinin receptor antagonists (HOE 140, NPC 17731) and other pharmacological agents to evaluate inhibitory effects.
- Dose-response analysis and statistical evaluation of results.
Main Results:
- Bradykinin induced a dose-related increase in pleural cell influx, peaking at 4 hours and persisting for up to 72 hours.
- Exudation was observed between 2 and 6 hours post-bradykinin administration.
- Specific bradykinin B2 receptor antagonists (HOE 140, NPC 17731) significantly inhibited bradykinin-induced cell influx, while Des-Arg9-[Leu8]bradykinin did not.
- Pre-treatment with indomethacin, terfenadine, dexamethasone, and other agents also significantly inhibited cell migration.
Conclusions:
- Bradykinin exerts a significant pro-inflammatory effect on the mouse pleural cavity.
- This effect is primarily mediated through the activation of bradykinin B2 receptors.
- Bradykinin-induced inflammation involves the release of secondary inflammatory mediators, as evidenced by the inhibitory effects of various drugs.