Costa Robson, Fernandes Elizabeth S, Menezes-de-Lima Octávio, Campos Maria M, Calixto João B
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88049-900 Florianópolis, SC, Brazil.
Peptides. 2006 Nov;27(11):2967-75. doi: 10.1016/j.peptides.2006.07.007. Epub 2006 Aug 17.
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.
两种新型选择性非肽类缓激肽B(1)受体拮抗剂，即苯二氮䓬拮抗剂和SSR240612，在角叉菜胶诱导的小鼠胸膜炎中进行了评估。肽类R-715（0.5毫克/千克，腹腔注射）和非肽类苯二氮䓬（3毫克/千克，腹腔注射）拮抗剂显著减少细胞迁移（主要是中性粒细胞），而不改变血浆渗出。SSR240612（1毫克/千克，腹腔注射）除了减少渗出外，还减少了总细胞数和中性粒细胞数。口服SSR240612（10毫克/千克）也降低了总细胞数和中性粒细胞计数。只有苯二氮䓬拮抗剂抑制了肺髓过氧化物酶活性。没有一种受试拮抗剂能显著改变肺和胸膜中肿瘤坏死因子α和白细胞介素-1β的产生。我们提供了关于非肽类B(1)受体拮抗剂体内抗炎作用的有趣证据。
