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<title lang=en>Functional expression and regulation of drug transporters in monolayer- and sandwich-cultured mouse hepatocytes.</title>
<creator>Noel, Grégory</creator>
<creator>Le Vee, Marc</creator>
<creator>Moreau, Amélie</creator>
<creator>Stieger, Bruno</creator>
<creator>Parmentier, Yannick</creator>
<creator>FARDEL, Olivier</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Contaminants Chimiques, immunité et Inflammation ; Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) - Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Laboratoire Pharmaceutique ; Technologie Servier</contributor>
<contributor>Department of Clinical Pharmacology and Toxicology ; Hôpital universitaire de Zurich</contributor>
<contributor>Contraintes et Apprentissage ; Laboratoire Pharmaceutique ; Technologie Servier - Technologie Servier</contributor>
<contributor>Contaminants Chimiques, immunité et Inflammation ; Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC) ; Université de Rennes 1 (UR1) - Hôpital Pontchaillou - CHU Pontchaillou [Rennes] - Université de Rennes 1 (UR1) - Hôpital Pontchaillou - CHU Pontchaillou [Rennes] - Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) - Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<description>International audience</description>
<source>ISSN: 0928-0987</source>
<source>European Journal of Pharmaceutical Sciences</source>
<publisher>Elsevier</publisher>
<identifier>inserm-00823243</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00823243</identifier>
<source>http://www.hal.inserm.fr/inserm-00823243</source>
<source>European Journal of Pharmaceutical Sciences, Elsevier, 2013, 49 (1), pp.39-50. 〈10.1016/j.ejps.2013.01.013〉</source>
<identifier>DOI : 10.1016/j.ejps.2013.01.013</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejps.2013.01.013</relation>
<identifier>PUBMED : 23396053</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/23396053</relation>
<language>en</language>
<subject lang=en>Drug transporters</subject>
<subject lang=en>Primary hepatocytes</subject>
<subject lang=en>Mouse</subject>
<subject lang=en>Monolayer</subject>
<subject lang=en>Sandwich</subject>
<subject lang=en>Regulation</subject>
<subject>[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Primary hepatocyte cultures are now considered as convenient models for in vitro analyzing liver drug transport. However, if primary human and rat hepatocytes have been well-characterized with respect to drug transporter expression and regulation, much less is known for primary mouse hepatocytes. The present study was therefore designed to gain insights about this point. The profile of sinusoidal and canalicular drug transporter mRNA expression in short time (4h)-cultured mouse hepatocytes was found to be highly correlated with that of freshly isolated hepatocytes; by contrast, those of counterparts cultured for a longer time (until 4days) either in monolayer configurations on plastic or collagen or in sandwich configuration with matrigel were profoundly altered: uptake drug transporters such as Oct1, Oatps and Oat2 were thus down-regulated, whereas most of efflux transporters such as Mdr1a/b, Mrp3, Mrp4 and Bcrp were induced. Moreover, short time-cultured hepatocytes exhibited the highest levels of sinusoidal influx transporter activities. Transporter-mediated drug secretion into canalicular networks was however only observed in sandwich-cultured hepatocytes. Mouse hepatocytes cultured either in monolayer or sandwich configurations were finally shown to exhibit up-regulation of referent transporters in response to exposure to prototypical activators of the drug sensing receptors pregnane X receptor, aryl hydrocarbon receptor or constitutive androstane receptor. Taken together, these data demonstrate the feasibility of using primary mouse hepatocytes for investigating potential interactions of xenobiotics with hepatic transporter activity or regulation, provided that adequate culture conditions are retained.</description>
<date>2013-02-06</date>
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