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dc.contributor.author
Alonso, Maria Natalia
dc.contributor.author
Fernández, Natalia Brenda
dc.contributor.author
Notcovich, Cintia Karina
dc.contributor.author
Monczor, Federico
dc.contributor.author
Simaan, May
dc.contributor.author
Baldi, Alberto
dc.contributor.author
Gutkind, J. Silvio
dc.contributor.author
Davio, Carlos Alberto
dc.contributor.author
Shayo, Carina Claudia
dc.date.available
2015-08-24T14:43:35Z
dc.date.issued
2013-05
dc.identifier.citation
Alonso, Maria Natalia; Fernández, Natalia Brenda; Notcovich, Cintia Karina; Monczor, Federico; Simaan, May; et al.; Cross-Desensitization and Cointernalization of H1 and H2 Histamine Receptors Reveal New Insights into Histamine Signal Integration; American Society for Pharmacology and Experimental Therapeutics; Molecular Pharmacology; 83; 5-2013; 1087-1098
dc.identifier.issn
0026-895X
dc.identifier.uri
http://hdl.handle.net/11336/1781
dc.description.abstract
G-protein coupled receptor (GPCR) signaling does not result from sequential activation of a linear pathway of proteins/enzymes, but rather from complex interactions of multiple, branched signaling routes, ie, signaling networks. In this work we present an exhaustive study of the crosstalk between H1 and H2 histamine receptors (H1R and H2R) in U937 cells and CHO transfected cells. By desensitization assays we demonstrated the existence of a cross-desensitization between both receptors independent of protein kinase A (PKA) or C (PKC). H1R agonist stimulation inhibited cell proliferation and induced apoptosis in U937 cells following treatment for 48h. H1R-induced antiproliferative and apoptotic response was inhibited by an H2R agonist suggesting that the crosstalk between both receptors modifies their function. Binding and confocal microscopy studies revealed cointernalization of both receptors upon treatment with the agonists. In order to evaluate potential heterodimerization of the receptors, sensitized emission FRET experiments were performed in HEK293T cells using H1R-CFP and H2R-YFP. To our knowledge these findings may represent the first demonstration of agonist-induced heterodimerization of the H1R and H2R. In addition, we also show that the inhibition of the internalization process did not prevent receptor cross-desensitization which was mediated by GRK2. Our study provides new insights into the complex signaling network mediated by histamine and further knowledge for the rational use of its ligands.
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
Histamine-Receptors
dc.subject
Heterodimerization
dc.subject
Cointernalization
dc.subject
Apoptosis
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Farmacología y Farmacia
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Cross-Desensitization and Cointernalization of H1 and H2 Histamine Receptors Reveal New Insights into Histamine Signal Integration
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
83
dc.journal.pagination
1087-1098
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Baltimore
dc.conicet.avisoEditorial
HighWire: final version free/ PubMed Central free full text. U.S. Government work not protected by U.S. copyright
dc.description.fil
Fil: Alonso, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina;
dc.description.fil
Fil: Fernández, Natalia Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina;
dc.description.fil
Fil: Notcovich, Cintia Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); 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: Simaan, May. National Institutes of Health; Estados Unidos de América;
dc.description.fil
Fil: Baldi, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina;
dc.description.fil
Fil: Gutkind, J. Silvio. National Institutes of Health; Estados Unidos de América;
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 (i); Argentina;
dc.journal.title
Molecular Pharmacology
dc.relation.isreferencedin
info:eu-repo/semantics/reference es info:eu-repo/semantics/reference/pmid/PMID: 23462507 [PubMed - indexed for MEDLINE] PMCID: PMC3629830 Free PMC Article
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://molpharm.aspetjournals.org/content/83/5/1087.full.pdf+html
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629830/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1124/mol.112.083394


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