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dc.contributor.author Ruiz, Maria Laura
dc.contributor.author Rigalli, Juan Pablo
dc.contributor.author Arias, Agostina
dc.contributor.author Villanueva, Silvina Stella Maris
dc.contributor.author Banchio, Claudia Elena
dc.contributor.author Vore, Mary
dc.contributor.author Mottino, Aldo Domingo
dc.contributor.author Catania, Viviana Alicia
dc.date.available 2016-06-08T16:14:51Z
dc.date.issued 2013-02
dc.identifier.citation Ruiz, Maria Laura; Rigalli, Juan Pablo; Arias, Agostina; Villanueva, Silvina Stella Maris; Banchio, Claudia Elena; et al.; Induction of hepatic multidrug resistance-associated protein 3 by ethynylestradiol is independent of cholestasis and mediated by estrogen receptor; American Society for Pharmacology and Experimental Therapeutics; Drug Metabolism and Disposition; 41; 2; 2-2013; 275-280
dc.identifier.issn 0090-9556
dc.identifier.uri http://hdl.handle.net/11336/6113
dc.description.abstract Multidrug resistance–associated protein 3 (Mrp3; Abcc3) expression and activity are up-regulated in rat liver after in vivo repeated administration of ethynylestradiol (EE), a cholestatic synthetic estrogen, whereas multidrug resistance-associated protein 2 (Mrp2) is down-regulated. This study was undertaken to determine whether Mrp3 induction results from a direct effect of EE, independent of accumulation of any endogenous common Mrp2/Mrp3 substrates resulting from cholestasis and the potential mediation of estrogen receptor (ER). In in vivo studies, male rats were given a single, noncholestatic dose of EE (5 mg/kg s.c.), and basal bile flow and the biliary excretion rate of bile salts and glutathione were measured 5 hours later. This treatment increased Mrp3 mRNA by 4-fold, detected by real-time polymerase chain reaction, despite the absence of cholestasis. Primary culture of rat hepatocytes incubated with EE (1–10 µM) for 5 hours exhibited a 3-fold increase in Mrp3 mRNA (10 µM), consistent with in vivo findings. The increase in Mrp3 mRNA by EE was prevented by actinomycin D, indicating transcriptional regulation. When hepatocytes were incubated with an ER antagonist [7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol (ICI182/780), 1 µM], in addition to EE, induction of Mrp3 mRNA was abolished, implicating ER as a key mediator. EE induced an increase in ER-α phosphorylation at 30 minutes and expression of c-Jun, a well-known ER target gene, at 60 minutes, as detected by Western blotting of nuclear extracts. These increases were prevented by ICI182/780. In summary, EE increased the expression of hepatic Mrp3 transcriptionally and independently of any cholestatic manifestation and required participation of an ER, most likely ER-α, through its phosphorylation.
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 MRP3·
dc.subject ESTROGEN RECEPTOR
dc.subject CHOLESTASIS
dc.subject ETHYNYLESTRADIOL
dc.subject.classification Farmacología y Farmacia
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Induction of hepatic multidrug resistance-associated protein 3 by ethynylestradiol is independent of cholestasis and mediated by estrogen receptor
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2016-03-21T18:22:50Z
dc.journal.volume 41
dc.journal.number 2
dc.journal.pagination 275-280
dc.journal.pais Estados Unidos
dc.journal.ciudad Baltimore
dc.description.fil Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Arias, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Banchio, Claudia Elena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
dc.description.fil Fil: Vore, Mary. University Of Kentucky; Estados Unidos
dc.description.fil Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.journal.title Drug Metabolism and Disposition
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://dmd.aspetjournals.org/content/41/2/275.long
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1124/dmd.112.047357
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/10.1124/dmd.112.047357
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/PMC3558861
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558861/


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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)