Evidence for activation of the tissue kallikrein-kinin system in nociceptive transmission and inflammatory responses of mice using a specific enzyme inhibitor

• Autor(a) principal: Emim, José AD
• Data de Publicação: 2000
• Outros Autores: Souccar, Caden [UNIFESP], Castro, Maria SD, Godinho, Rosely Oliveira [UNIFESP], Cezari, Maria HS, Juliano, Luiz [UNIFESP], Lapa, Antonio José [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1038/sj.bjp.0703362; http://repositorio.unifesp.br/handle/11600/26331
• topic: tissue kallikrein inhibitor; kinins; nociception; inflammation

1 the pharmacological activity of phenylacetyl-Phe-Ser-Arg-N-(2,4-dinitrophenyl)-ethylenediamine (TKI), a tissue kallikrein specific inhibitor, was assessed using models of nociception and inflammation in mice.2 Injection of TKI (13.6-136 mu mol kg(-1), i.p. or 41-410 mu mol kg(-1), s.c.) produced a dose-related inhibition of the acetic acid-induced writhes (by 37 to 85% or 34 to 80%, respectively). the antinociceptive activity of TKI (41 mu mol kg(-1), i.p.) was maximal after 30 min injection and lasted for 120 min. the effect was unaltered by pretreatment with naloxone (8.2 mu mol kg(-1), s.c.) or bilateral adrenalectomy.3 TRI (41 and 136 mu mol kg(-1), i.p.) produced a dose-related decrease of the late phase of formalin-induced nociception by 79 and 98%, respectively. At 136 mu mol kg(-1), i.p., TKI also shortened the duration of paw licking in the early phase by 69%. TKI (41 and 136 mu mol kg(-1), i.p.) also reduced the capsaicin-induced nociceptive response (by 51 to 79%).4 TKI (41 pmol kg(-1), i.p. or 410 mu mol kg(-1), s.c.) reduced the oedematogenic response, from the second to the fifth hour after carrageenin injection by 36 to 30% or by 47 to 39%, respectively.5 Pretreatment with TKI (41 mu mol kg(-1), i.p.) reduced the capsaicin-induced neurogenic inflammation in the mouse ear by 54%.6 It is concluded that TKI presents antinociceptive and antiinflammatory activities mediated by inhibition of kinin formation by tissue kallikrein in mice. the results also indicate that the tissue kallikrein-dependent pathway contributes to kinin generation in nociceptive and inflammatory processes in mice.