Functional assessment of angiotensin II and bradykinin analogues containing the paramagnetic amino acid TOAC

Página do item simplificado
dc.contributor.authorSantos, Edson L. [UNIFESP]
dc.contributor.authorSouza, Kely de Picoli [UNIFESP]
dc.contributor.authorSabatini, Regiane A. [UNIFESP]
dc.contributor.authorMartin, Renan P. [UNIFESP]
dc.contributor.authorFernandes, Litiam [UNIFESP]
dc.contributor.authorNardi, Daniela T. [UNIFESP]
dc.contributor.authorMalavolta, Luciana [UNIFESP]
dc.contributor.authorShimuta, Suma I. [UNIFESP]
dc.contributor.authorNakaie, Clovis R. [UNIFESP]
dc.contributor.authorPesquero, Joao B. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:49:32Z
dc.date.available2016-01-24T13:49:32Z
dc.date.issued2008-02-01
dc.description.abstractThis study characterized pharmacologically the functional responses to agonists angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-Noxyl-4-amino-4-carboxylic acid) spin [abet at the N-terminal (TOAC(1)-AngII and TOAC(0)-BK) and internal (TOAC(3)-AngII and TOAC(3)-BK) positions of these vasoactive peptides. Affinity constants of the ligands for AT(1) and B-2 receptors were evaluated in vitro by binding assays and biological effects by extracellular acidification rates and in vivo by blood pressure responses. in contrast to internally labeled analogues (TOAC(3)-AngII or TOAC(3)-BK), the TOAC(1)-AngII and TOAC(0)-BK derivatives dose-dependently increased the extracellular acidification rate in adherent cultured Chinese hamster ovary (CHO) cells expressing AT, or B2 receptors, respectively. in addition, TOAC(1)-AngII induced an increase in blood pressure when injected intravenously in awaken rats although with a potency four times smaller when compared to native AngII. Similarly to BK, TOAC(0)-BK dose-dependently decreased blood pressure when injected intra-arterially in rats with a lower potency when compared to the native peptide. On the contrary, TOAC(3)-AngII or TOAC(3)-BK did not provoke any alteration in blood pressure levels. in summary, our results confirmed that the insertion of TOAC-probe in the N-terminal region of peptides does not significantly modify the affinity or biological activity in vitro and in vivo conditions and could be an important toool to evaluate peptide-receptor interaction mechanism. Conversely, possibly due to the unique bend-inducing property of the cyclic TOAC probe, its insertion at position 3 in both AngII and BK structures seems to restrict the interaction and the activation of the AT, and B2 receptors. (c) 2007 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent293-299
dc.identifierhttp://dx.doi.org/10.1016/j.intimp.2007.07.029
dc.identifier.citationInternational Immunopharmacology. Amsterdam: Elsevier B.V., v. 8, n. 2, p. 293-299, 2008.
dc.identifier.doi10.1016/j.intimp.2007.07.029
dc.identifier.issn1567-5769
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30420
dc.identifier.wosWOS:000253025700029
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofInternational Immunopharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectTOACen
dc.subjectangiotensin IIen
dc.subjectbradykininen
dc.subjectbindingen
dc.subjectG-protein coupled receptorsen
dc.titleFunctional assessment of angiotensin II and bradykinin analogues containing the paramagnetic amino acid TOACen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
Em verificação - Geral