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dc.contributor.author
Alonso, Natalia
dc.contributor.author
Zappia, Carlos Daniel
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Cabrera, Maia Diana Eliana
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Davio, Carlos Alberto
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Shayo, Carina Claudia
dc.contributor.author
Monczor, Federico
dc.contributor.author
Fernandez, Natalia Cristina
dc.date.available
2017-03-30T19:13:27Z
dc.date.issued
2015-03
dc.identifier.citation
Alonso, Natalia; Zappia, Carlos Daniel; Cabrera, Maia Diana Eliana; Davio, Carlos Alberto; Shayo, Carina Claudia; et al.; Physiological implications of biased signaling at histamine H2 receptors; Frontiers; Frontiers in Pharmacology; 6; 3-2015; 1-9; 45
dc.identifier.uri
http://hdl.handle.net/11336/14550
dc.description.abstract
Histamine mediates numerous functions acting through its four receptor subtypes all belonging to the large family of seven transmembrane G-protein coupled receptors. In particular, histamine H2 receptor (H2R) is mainly involved in gastric acid production, becoming a classic pharmacological target to treat Zollinger–Ellison disease and gastric and duodenal ulcers. H2 ligands rank among the most widely prescribed and over the counter-sold drugs in the world. Recent evidence indicate that some H2R ligands display biased agonism, selecting and triggering some, but not all, of the signaling pathways associated to the H2R. The aim of the present work is to study whether famotidine, clinically widespread used ligand acting at H2R, exerts biased signaling. Our findings indicate that while famotidine acts as inverse agonist diminishing cAMP basal levels, it mimics the effects of histamine and the agonist amthamine concerning receptor desensitization and internalization. Moreover, the treatment of HEK293T transfected cells with any of the three ligands lead to a concentration dependent pERK increment. Similarly in AGS gastric epithelial cells, famotidine treatment led to both, the reduction in cAMP levels as well as the increment in ERK phosphorylation, suggesting that this behavior could have pharmacological relevant implications. Based on that, histidine decarboxylase expression was studied by quantitative PCR in AGS cells and its levels were increased by famotidine as well as by histamine and amthamine. In all cases, the positive regulation was impeded by the MEK inhibitor PD98059, indicating that biased signaling toward ERK1/2 pathway is the responsible of such enzyme regulation. These results support that ligand bias is not only a pharmacological curiosity but has physiological and pharmacological implications on cell metabolism.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
7tmr
dc.subject
H2r Ligands
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Biased Agonism
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Pluridimensional Efficacy
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Gpcr
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Internalization
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Erk
dc.subject
Hdc
dc.subject.classification
Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Physiological implications of biased signaling at histamine H2 receptors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-07T15:20:27Z
dc.identifier.eissn
1663-9812
dc.journal.volume
6
dc.journal.pagination
1-9; 45
dc.journal.pais
Suiza
dc.journal.ciudad
Lausana
dc.description.fil
Fil: Alonso, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil
Fil: Zappia, Carlos Daniel. 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: Cabrera, Maia Diana Eliana. 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: 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. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina; Argentina
dc.description.fil
Fil: Shayo, Carina Claudia. 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: 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; Argentina
dc.journal.title
Frontiers in Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fphar.2015.00045/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fphar.2015.00045
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