The relevance of kinin B(1) receptor upregulation in a mouse model of colitis

The relevance of kinin B(1) receptor upregulation in a mouse model of colitis

Autor Hara, D. B. Google Scholar
Leite, D. F. P. Google Scholar
Fernandes, E. S. Google Scholar
Passos, G. F. Google Scholar
Guimaraes, Alessander de Oliveira Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Campos, M. M. Google Scholar
Calixto, J. B. Google Scholar
Instituição Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Pontificia Univ Catolica Rio Grande do Sul
Resumo Background and purpose: Kinins are implicated in many pathophysiological conditions, and recent evidence has suggested their involvement in colitis. This study assessed the role of the kinin B(1) receptors in a mouse model of colitis.Experimental approach: Colitis was induced in mice by 2,4,6-trinitrobenzene sulphonic acid (TNBS), and tissue damage and myeloperoxidase activity were assessed. B(1) receptor induction was analysed by organ bath studies, binding assay and reverse transcription PCR.Key results: TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of colon B(1) receptor-mediated contraction, with the maximal response observed at 72 h. the upregulation of the B(1) receptor at this time point was also confirmed by means of binding studies. B(1) receptor mRNA levels were elevated as early as 6 h after colitis induction and remained high for up to 48 h. TNBS-evoked tissue damage and neutrophil influx were reduced by the selective B(1) receptor antagonist SSR240612, and in B(1) receptor knockout mice. in vivo treatment with inhibitors of protein synthesis, nuclear factor-kappa B activation, inducible nitric oxide synthase (iNOS) or tumour necrosis factor alpha (TNF alpha) significantly reduced B(1) receptor agonist-induced contraction. Similar results were observed in iNOS and TNF receptor 1-knockout mice.Conclusions and implications: These results provide convincing evidence on the role of B1 receptors in the pathogenesis of colitis. Therefore, the blockade of kinin B1 receptors might represent a new therapeutic option for treating inflammatory bowel diseases.
Assunto inflammation
kinin B(1) receptor
pro-inflammatory peptides
inflammatory bowel disease treatment
Idioma Inglês
Data 2008-07-01
Publicado em British Journal of Pharmacology. Malden: Wiley-Blackwell, v. 154, n. 6, p. 1276-1286, 2008.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 1276-1286
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000257613300012

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