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Analysis of the inflammatory response induced by substance P in the mouse pleural cavity
T S Fröde-Saleh1, J B Calixto, Y S Medeiros
1Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Abstract:
This study analyzes both cell migration and exudation responses elicited by substance P (SP) in the mouse pleural cavity. SP caused, 4 h after its administration into the mouse pleural cavity, a dose-related recruitment of leukocytes (ED50 = 14.2 nmol), mainly due to mononuclears. Leukocytes peaked between 2 and 4 h, being followed by a slight decay that remained elevated for up to 24 h. Exudation, although small, was significantly elevated from 2 to 96 h after. NK1 (FK 888) or NK3 (SR 142801), but not NK2 (SR 48968) tachykinin receptor antagonists, significantly inhibited cell migration. HOE 140 and NPC 17731, bradykinin B2 receptor antagonists, caused graded inhibition of cell influx (ID50s of 0.03 and 0.04 pmol), but des-Arg9-Leu8-BK, B1 receptor antagonist, had no effect. The nitric oxide inhibitors L-NOARG and L-NAME, but not D-NAME, significantly inhibited SP-induced pleurisy. Pretreatment of the animals with indomethacin, dexamethasone, terfenadine, theophylline or salbutamol produced significant inhibition of the inflammatory parameters, whereas cromolyn only inhibited exudation. These results indicate that intrapleural injection of SP in mice elicit a long-lasting inflammatory reaction that is characterized by the participation of nitric oxide, kinins, cyclooxygenase metabolites and histamine. Antiasthmatic drugs such as theophylline, salbutamol, dexamethasone, and, to a lesser extent cromolyn, also markedly inhibit this inflammatory reaction. These results provide clear evidence supporting the role played by SP in neurogenic inflammation.
Insights
Substance P (SP) triggers a prolonged inflammatory response in mouse pleural cavities, involving cell migration and exudation. This reaction is mediated by nitric oxide, kinins, and histamine, and is inhibited by certain antiasthmatic drugs.
Area of Science:
- Immunology
- Pharmacology
- Inflammation Research
Background:
- Substance P (SP) is a neuropeptide implicated in inflammatory processes.
- Neurogenic inflammation involves the release of mediators like SP.
- Understanding SP's role in pleural inflammation is crucial for therapeutic development.
Purpose of the Study:
- To investigate the effects of SP on cell migration and exudation in the mouse pleural cavity.
- To identify the specific receptors and inflammatory mediators involved in SP-induced pleurisy.
- To evaluate the efficacy of various drugs, including antiasthmatics, in inhibiting SP-induced inflammation.
Main Methods:
- Intrapleural administration of substance P (SP) in mice.
- Dose-response analysis of leukocyte recruitment and exudation.
- Use of specific receptor antagonists (NK1, NK2, NK3, bradykinin B1/B2) and enzyme inhibitors (nitric oxide synthase, cyclooxygenase).
- Assessment of anti-inflammatory effects of drugs like indomethacin, dexamethasone, theophylline, and salbutamol.
Main Results:
- SP induced a dose-related leukocyte influx, primarily mononuclear cells, peaking at 2-4 hours and lasting up to 24 hours.
- Significant exudation was observed for up to 96 hours.
- NK1 and NK3 receptor antagonists, but not NK2, inhibited cell migration.
- Bradykinin B2 receptor antagonists significantly inhibited cell influx.
- Nitric oxide synthase inhibitors (L-NOARG, L-NAME) reduced SP-induced pleurisy.
- Indomethacin, dexamethasone, terfenadine, theophylline, and salbutamol significantly inhibited inflammatory parameters; cromolyn only inhibited exudation.
Conclusions:
- Intrapleural SP elicits a sustained inflammatory reaction involving nitric oxide, kinins, cyclooxygenase metabolites, and histamine.
- SP-induced neurogenic inflammation in the mouse pleural cavity is mediated via NK1/NK3 and bradykinin B2 receptors.
- Antiasthmatic drugs demonstrate significant inhibitory effects on SP-induced inflammation, highlighting their therapeutic potential.