Functional expression and regulation of drug transporters in monolayer- and sandwich-cultured mouse hepatocytes.

Grégory Noel 1 Marc Le Vee 2 Amélie Moreau 3 Bruno Stieger 4 Yannick Parmentier 5 Olivier Fardel 6, *
* Auteur correspondant
2 Contaminants Chimiques, immunité et Inflammation
Irset - Institut de recherche, santé, environnement et travail [Rennes]
5 Contraintes et Apprentissage
Laboratoire Pharmaceutique
6 Contaminants Chimiques, immunité et Inflammation
HITC - Service d'Hématologie, Immunologie et de Thérapie Cellulaire, Irset - Institut de recherche, santé, environnement et travail [Rennes]
Abstract : 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.
Type de document :
Article dans une revue
European Journal of Pharmaceutical Sciences, Elsevier, 2013, 49 (1), pp.39-50. 〈10.1016/j.ejps.2013.01.013〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00823243
Contributeur : Nathalie Coval <>
Soumis le : jeudi 16 mai 2013 - 14:28:19
Dernière modification le : jeudi 21 décembre 2017 - 13:28:04

Identifiants

Citation

Grégory Noel, Marc Le Vee, Amélie Moreau, Bruno Stieger, Yannick Parmentier, et al.. Functional expression and regulation of drug transporters in monolayer- and sandwich-cultured mouse hepatocytes.. European Journal of Pharmaceutical Sciences, Elsevier, 2013, 49 (1), pp.39-50. 〈10.1016/j.ejps.2013.01.013〉. 〈inserm-00823243〉

Partager

Métriques

Consultations de la notice

191