title: Analysis of the inflammatory response induced by substance P in the mouse pleural cavity.
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.
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: T S
authors.initials: TS
authors.lastname: Fröde-Saleh
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
authors.forename: Y S
authors.initials: YS
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D005122:Exudates and Transudates; D005260:Female; D018836:Inflammation Mediators; D007963:Leukocytes, Mononuclear; D008297:Male; D051379:Mice; D020078:Neurogenic Inflammation / Q000209:etiology; D010994:Pleura / Q000187:drug effects; D010998:Pleurisy / Q000139:chemically induced*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D013373:Substance P / Q000494:pharmacology*
chemical_list: D018836:Inflammation Mediators; D018039:Receptors, Tachykinin; D013373:Substance P