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dc.contributor.author Alonso, Natalia
dc.contributor.author Zappia, Carlos Daniel
dc.contributor.author Cabrera, Maia Diana Eliana
dc.contributor.author Davio, Carlos Alberto
dc.contributor.author 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
dc.subject BIASED AGONISM
dc.subject PLURIDIMENSIONAL EFFICACY
dc.subject GPCR
dc.subject INTERNALIZATION
dc.subject ERK
dc.subject HDC
dc.subject.classification Farmacología y Farmacia
dc.subject.classification Medicina Básica
dc.subject.classification 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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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)