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

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dc.contributor.authorHara, D. B.
dc.contributor.authorLeite, D. F. P.
dc.contributor.authorFernandes, E. S.
dc.contributor.authorPassos, G. F.
dc.contributor.authorGuimaraes, Alessander de Oliveira [UNIFESP]
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorCampos, M. M.
dc.contributor.authorCalixto, J. B.
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionPontificia Univ Catolica Rio Grande do Sul
dc.date.accessioned2016-01-24T13:51:29Z
dc.date.available2016-01-24T13:51:29Z
dc.date.issued2008-07-01
dc.description.abstractBackground 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.en
dc.description.affiliationUniv Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, BR-88049900 Florianopolis, SC, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationPontificia Univ Catolica Rio Grande do Sul, Dept Surg, Fac Dent, Porto Alegre, RS, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1276-1286
dc.identifierhttp://dx.doi.org/10.1038/bjp.2008.212
dc.identifier.citationBritish Journal of Pharmacology. Malden: Wiley-Blackwell, v. 154, n. 6, p. 1276-1286, 2008.
dc.identifier.doi10.1038/bjp.2008.212
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30744
dc.identifier.wosWOS:000257613300012
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectinflammationen
dc.subjectkinin B(1) receptoren
dc.subjectcolitisen
dc.subjectpro-inflammatory peptidesen
dc.subjectinflammatory bowel disease treatmenten
dc.titleThe relevance of kinin B(1) receptor upregulation in a mouse model of colitisen
dc.typeinfo:eu-repo/semantics/article
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