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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·
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Estrogen Receptor
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Cholestasis
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Ethynylestradiol
dc.subject.classification
Farmacología y Farmacia
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Medicina Básica
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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/10.1124/dmd.112.047357
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/url/PMC3558861
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558861/


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