The non-peptide kinin receptor antagonists FR 173657 and SSR 240612: Preclinical evidence for the treatment of skin inflammation

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dc.contributor.authorPietrovski, Evelise Fernandes
dc.contributor.authorOtuki, Michel Fleith
dc.contributor.authorRegoli, Domenico
dc.contributor.authorBader, Michael
dc.contributor.authorPesquero, Joao Bosco [UNIFESP]
dc.contributor.authorCabrini, Daniela Almeida
dc.contributor.authorZampronio, Aleksander Roberto
dc.contributor.institutionUniv Fed Parana
dc.contributor.institutionUniv Estadual Ponta Grossa
dc.contributor.institutionUniv Ferrara
dc.contributor.institutionMax Delbruck Ctr Mol Med MDC
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:52:11Z
dc.date.available2016-01-24T13:52:11Z
dc.date.issued2009-01-08
dc.description.abstractPeptide and non-peptide kinin receptor antagonists were evaluated in cutaneous inflammation models in mice. Topical and i.p. application of kinin B(1) and B(2) receptor antagonists caused a significant inhibition of the capsaicin-induced cutaneous neurogenic inflammatory response. the calculated mean ID(50) for Hoe140 and SSR240612 were 23.83 (9.14-62.14) nmol/kg and 0.23 (0.15-0.36) mg/ear, respectively. the I(max) observed for Hoe140, SSR240612, R-715, FR173657, and FR plus SSR were 61 +/- 5%. 56 +/- 3%, 65 +/- 10%, 48 +/- 8%, and 52 +/- 4%, respectively. Supporting these results, double B(1) and B(2) kinin receptors knockout mice showed a significant inhibition of capsaicin-induced ear oedema (42 +/- 7%). However, mice with a single deletion of either B(1) or B(2) receptors exhibited no change in their capsaicin responses. in contrast, all of the examined kinin receptor antagonists were unable to inhibit the oedema induced by TPA and the results from knockout mice confirmed the lack of kinin receptor signaling in this model. These findings show that kinin receptors are present in the skin and that both kinin receptors seem to be important in the neurogenic inflammatory response. Moreover, non-peptide antagonists were very effective in reducing skin inflammation when topically applied, thereby suggesting that they could be useful tools in the treatment of some skin inflammatory diseases. (C) 2008 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Parana, Setor Ciencias Biol, Dept Pharmacol, Ctr Politecn, BR-81530900 Curitiba, Parana, Brazil
dc.description.affiliationUniv Estadual Ponta Grossa, Dept Pharmaceut Sci, Panta Grossa, Parana, Brazil
dc.description.affiliationUniv Ferrara, Dept Expt & Clin Med, I-44100 Ferrara, Italy
dc.description.affiliationMax Delbruck Ctr Mol Med MDC, Berlin, Germany
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent67-72
dc.identifierhttp://dx.doi.org/10.1016/j.regpep.2008.10.005
dc.identifier.citationRegulatory Peptides. Amsterdam: Elsevier B.V., v. 152, n. 1-3, p. 67-72, 2009.
dc.identifier.doi10.1016/j.regpep.2008.10.005
dc.identifier.issn0167-0115
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31246
dc.identifier.wosWOS:000262748500011
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofRegulatory Peptides
dc.rightsAcesso restrito
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectCapsaicinen
dc.subjectEar oedemaen
dc.subjectKinin receptorsen
dc.subjectKnockout miceen
dc.subjectSSR240612en
dc.subjectFR173657en
dc.titleThe non-peptide kinin receptor antagonists FR 173657 and SSR 240612: Preclinical evidence for the treatment of skin inflammationen
dc.typeArtigo
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