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dc.contributor.author Fernandez, Natalia Cristina
dc.contributor.author Monczor, Federico
dc.contributor.author Baldi, Alberto
dc.contributor.author Davio, Carlos Alberto
dc.contributor.author Shayo, Carina Claudia
dc.date.available 2017-10-04T18:21:23Z
dc.date.issued 2008
dc.identifier.citation Fernandez, Natalia Cristina; Monczor, Federico; Baldi, Alberto; Davio, Carlos Alberto; Shayo, Carina Claudia; Histamine H2 receptor trafficking: role of arrestin, dynamin and clathrin in histamine H2 receptor internalization; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 74; 4; -1-2008; 1109-1118
dc.identifier.issn 0026-895X
dc.identifier.uri http://hdl.handle.net/11336/25894
dc.description.abstract Agonist-induced internalization of G protein-coupled receptors (GPCRs) has been implicated in receptor desensitization, resensitization, and down-regulation. In the present study, we sought to establish whether the histamine H2 receptor (H2r) agonist amthamine, besides promoting receptor desensitization, induced H2r internalization. We further studied the mechanisms involved and its potential role in receptor resensitization. In COS7 transfected cells, amthamine induced H2r time-dependent internalization, showing 70% of receptor endocytosis after 60-min exposure to amthamine. Agonist removal led to the rapid recovery of resensitized receptors to the cell surface. Similar results were obtained in the presence of cycloheximide, an inhibitor of protein synthesis. Treatment with okadaic acid, an inhibitor of the protein phosphatase 2A (PP2A) family of phosphatases, reduced the recovery of both H2r membrane sites and cAMP response. Arrestin 3 but not arrestin 2 overexpression reduced both H2r membrane sites and H2r-evoked cAMP response. Receptor cotransfection with dominant-negative mutants for arrestin, dynamin, Eps15 (a component of the clathrin-mediated endocytosis machinery), or RNA interference against arrestin 3 abolished both H2r internalization and resensitization. Similar results were obtained in U937 cells endogenously expressing H2r. Our findings suggest that amthamine-induced H2r internalization is crucial for H2r resensitization, processes independent of H2r de novo synthesis but dependent on PP2A-mediated dephosphorylation. Although we do not provide direct evidence for H2r interaction with beta-arrestin, dynamin, and/or clathrin, our results support their involvement in H2r endocytosis. The rapid receptor recycling to the cell surface and the specific involvement of arrestin 3 in receptor internalization further suggest that the H2r belongs to class A GPCRs.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Society for Pharmacology and Experimental Therapeutics
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject H2 HISTAMINE RECEPTOR
dc.subject DESESITIZATION
dc.subject INTERNALIZATION
dc.subject ARRESTIN
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Histamine H2 receptor trafficking: role of arrestin, dynamin and clathrin in histamine H2 receptor internalization
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-09-25T18:30:55Z
dc.identifier.eissn 1521-0111
dc.journal.volume 74
dc.journal.number 4
dc.journal.pagination 1109-1118
dc.journal.pais Estados Unidos
dc.journal.ciudad Bethesda
dc.description.fil Fil: Fernandez, Natalia Cristina. 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
dc.description.fil Fil: 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.description.fil Fil: Baldi, Alberto. 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.description.fil Fil: 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.description.fil Fil: 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.journal.title Molecular Pharmacology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/74/4/1109
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1124/mol.108.045336
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/pmid/18617631


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)