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dc.provenanceCONICET-
dc.creatorAlonso, Natalia-
dc.creatorMonczor, Federico-
dc.creatorEcheverría, Emiliana Beatriz-
dc.creatorDavio, Carlos Alberto-
dc.creatorShayo, Carina Claudia-
dc.creatorFernández, Natalia Brenda-
dc.date2017-08-24T20:25:16Z-
dc.date2017-08-24T20:25:16Z-
dc.date2014-04-01-
dc.date2017-08-08T14:24:25Z-
dc.date.accessioned2019-04-29T15:38:39Z-
dc.date.available2019-04-29T15:38:39Z-
dc.date.issued2014-04-01-
dc.identifierAlonso, Natalia; Monczor, Federico; Echeverría, Emiliana Beatriz; Davio, Carlos Alberto; Shayo, Carina Claudia; et al.; Signal transduction mechanism of biased ligands at histamine H2 receptors; Portland Press; Biochemical Journal; 459; 1; 1-4-2014; 117-126-
dc.identifier0264-6021-
dc.identifierhttp://hdl.handle.net/11336/22969-
dc.identifier1470-8728-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/298376-
dc.description7TMRs (seven-transmembrane receptors) exist as conformational collections in which different conformations would lead to differential downstream behaviours such as receptor phosphorylation, G-protein activation and receptor internalization. In this context, a ligand may cause differential activation of some, but not all, of the signalling events, which are associated to a particular receptor, and it would lead to biased agonism. The aim of the present study was to investigate whether H2R (histamine H2 receptor) ligands, described as inverse agonists because of their negative efficacy at modulating adenylate cyclase, could display some positive efficacy concerning receptor desensitization, internalization or even signalling through an adenylate-cyclase-independent pathway. Our present findings indicate that treatment with H2R inverse agonists leads to receptor internalization in HEK (human embryonic kidney)-293T transfected cells, by a mechanism mediated by arrestin and dynamin, but independent of GRK2 (G-protein-coupled receptor kinase 2)-mediated phosphorylation. On the other hand, we prove that two of the H2R inverse agonists tested, ranitidine and tiotidine, also induce receptor desensitization. Finally, we show that these ligands are able to display positive efficacy towards the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway by a mechanism that involves Gβγ and PI3K (phosphoinositide 3-kinase)-mediated signalling in both transfected HEK-293T cells and human gastric adenocarcinoma cells. These results point to the aspect of pluridimensional efficacy at H2R as a phenomenon that could be extended to naïve cells, and challenge previous classification of pharmacologically relevant histaminergic ligands.-
dc.descriptionFil: Alonso, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina-
dc.descriptionFil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Echeverría, Emiliana Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina-
dc.descriptionFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina-
dc.descriptionFil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina-
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dc.languageeng-
dc.publisherPortland Press-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.biochemj.org/content/459/1/117-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1042/BJ20131226-
dc.relationinfo:eu-repo/semantics/altIdentifier/pmid/24417223-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.source.urihttp://hdl.handle.net/11336/22969-
dc.subjectGPCR-
dc.subjectBIASED-AGONISM-
dc.subjectEFFICACY-
dc.subjectHISTAMINE-
dc.subjectBioquímica y Biología Molecular-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleSignal transduction mechanism of biased ligands at histamine H2 receptors-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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