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

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

Autor Emim, José AD Google Scholar
Souccar, Caden Autor UNIFESP Google Scholar
Castro, Maria SD Google Scholar
Godinho, Rosely Oliveira Autor UNIFESP Google Scholar
Cezari, Maria HS Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Lapa, Antonio José Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Palavra-chave tissue kallikrein inhibitor
kinins
nociception
inflammation
Idioma Inglês
Data de publicação 2000-07-01
Publicado em British Journal of Pharmacology. Basingstoke: Nature Publishing Group, v. 130, n. 5, p. 1099-1107, 2000.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Publicador Nature Publishing Group
Extensão 1099-1107
Fonte http://dx.doi.org/10.1038/sj.bjp.0703362
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000088067100018
Endereço permanente http://repositorio.unifesp.br/handle/11600/26331

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