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dc.contributor.author Shayo, Carina Claudia
dc.contributor.author Fernandez, Natalia Cristina
dc.contributor.author Lemos Legnazzi, Bibiana
dc.contributor.author Monczor, Federico
dc.contributor.author Mladovan, Alejandro
dc.contributor.author Baldi, Alberto
dc.contributor.author Davio, Carlos Alberto
dc.date.available 2017-12-22T05:25:40Z
dc.date.issued 2001-11
dc.identifier.citation Davio, Carlos Alberto; Baldi, Alberto; Mladovan, Alejandro; Monczor, Federico; Lemos Legnazzi, Bibiana; Fernandez, Natalia Cristina; et al.; Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 60; 5; 11-2001; 1049-1056
dc.identifier.issn 0026-895X
dc.identifier.uri http://hdl.handle.net/11336/31340
dc.description.abstract The histamine H2 receptor (H2r) belongs to the heptahelical receptor family; upon agonist binding, members of this family activate a G protein and the downstream effector adenylyl cyclase. Like other G protein-coupled receptors, exposure of H2r to agonists produces a desensitization of the response. The present study focused on the desensitization mechanism of this receptor. Using transiently transfected COS-7 cells expressing tagged-H2r, the desensitization induced by<br />amthamine, characterized by decreased cAMP production, was studied. Results show that the receptor was rapidly desensitized with a t1/2 0.49 0.01 min. Because of the rapid nature of H2r desensitization, receptor phosphorylation was examined as a likely mechanism for signal attenuation. H2r desensitization was not affected by protein kinases A and C (PKA and PKC) inhibitors but was remarkably reduced by Zn2, an inhibitor of G protein-coupled receptor kinases (GRKs). Cotransfection experiments using tagged H2r and different GRKs (2, 3, 5, or 6), demonstrated that GRK2 and GRK3 were the most potent in augmenting desensitization, causing a reduction in the maximal response to   amthamine and a decrease of the t1/2 for desensitization, whereas GRK5 and GRK6 did not affect the signaling. Receptor phosphorylation correlates with desensitization for each GRK studied, whereas phosphorylation that is dependent on protein kinases A and C seemed irrelevant in receptor signal termination. These results indicate that in H2rtransfected COS-7 cells, exposure to an agonist caused desensitization controlled by H2r phosphorylation via GRK2 and GRK3.
dc.format application/pdf
dc.language.iso eng
dc.publisher American Society for Pharmacology and Experimental Therapeutics
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject H2 HISTAMINE RECEPTOR
dc.subject DESENSITIZATION
dc.subject GRKs
dc.subject.classification Inmunología
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-12-04T18:00:17Z
dc.identifier.eissn 1521-0111
dc.journal.volume 60
dc.journal.number 5
dc.journal.pagination 1049-1056
dc.journal.pais Estados Unidos
dc.journal.ciudad Bethesda
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. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil Fil: Fernandez, Natalia Cristina. 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; Argentina
dc.description.fil Fil: Lemos Legnazzi, Bibiana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentina
dc.description.fil Fil: Monczor, Federico. 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: Mladovan, Alejandro. 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: 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 Fisicomatemática. Cátedra de Física; Argentina
dc.journal.title Molecular Pharmacology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/60/5/1049.long
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1124/mol.60.5.1049
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/11641433


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info:eu-repo/semantics/openAccess 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)