title: Effect of novel selective non-peptide kinin B(1) receptor antagonists on mouse pleurisy induced by carrageenan.
abstract: Two novel selective non-peptide kinin B(1) receptor antagonists, the benzodiazepine antagonist and SSR240612, were evaluated in carrageenan-induced mouse pleurisy. The peptide R-715 (0.5 mg/kg, i.p.) and the non-peptide benzodiazepine (3 mg/kg, i.p.) antagonists significantly decreased cellular migration (predominantly neutrophils), without altering plasma exudation. SSR240612 (1 mg/kg, i.p.) diminished total cells and neutrophils, besides exudation. Oral administration of SSR240612 (10 mg/kg) also reduced total cell and neutrophil counts. Only the benzodiazepine antagonist inhibited the lung myeloperoxidase activity. No tested antagonist significantly altered the lung and pleural TNFalpha and IL-1beta production. We provide interesting evidence on the anti-inflammatory in vivo effects of non-peptide B(1) receptor antagonists.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88049-900 Florianópolis, SC, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Costa
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
authors.forename: Octávio
authors.initials: O
authors.lastname: Menezes-de-Lima
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D002351:Carrageenan; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D053583:Interleukin-1beta / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles; D053583:Interleukin-1beta; C120984:R 715; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D002351:Carrageenan; D009195:Peroxidase; D001920:Bradykinin