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<title lang=en>The mitochondrial fluorescent dye rhodamine 123 is a high-affinity substrate for organic cation transporters (OCTs) 1 and 2.</title>
<creator>Jouan, Elodie</creator>
<creator>Le Vee, Marc</creator>
<creator>Denizot, Claire</creator>
<creator>Da Violante, Georges</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>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: 0767-3981</source>
<source>EISSN: 1472-8206</source>
<source>Fundamental and Clinical Pharmacology</source>
<publisher>Wiley-Blackwell</publisher>
<publisher>Wiley</publisher>
<identifier>inserm-00872840</identifier>
<identifier>http://www.hal.inserm.fr/inserm-00872840</identifier>
<source>http://www.hal.inserm.fr/inserm-00872840</source>
<source>Fundamental and Clinical Pharmacology, Wiley, 2012, 28 (1), pp.65-77. 〈10.1111/j.1472-8206.2012.01071.x〉</source>
<identifier>DOI : 10.1111/j.1472-8206.2012.01071.x</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1472-8206.2012.01071.x</relation>
<identifier>PUBMED : 22913740</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/22913740</relation>
<language>en</language>
<subject lang=en>rhodamine 123</subject>
<subject lang=en>organic cation transporter 2</subject>
<subject lang=en>organic cation transporter 1</subject>
<subject lang=en>drug transport</subject>
<subject>[SDV.BC] Life Sciences [q-bio]/Cellular Biology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Rhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 and OCT2. Intracellular uptake of the dye was demonstrated to be enhanced in both hOCT1- and hOCT2-overexpressing HEK293 cells when compared with control HEK293 cells. This increase of rhodamine 123 influxes was found to be a saturable carrier-mediated process, with low K(m) values (K(m) = 0.54 μm and K(m ) = 0.61 μm for transport of the dye in hOCT1- and hOCT2-positive HEK293 cells, respectively). Known inhibitors of hOCT1 and hOCT2 activities such as verapamil, amitriptyline, prazosin, and quinine were next demonstrated to decrease rhodamine 123 accumulation in hOCT1- and hOCT2-overexpressing HEK293 cells. In addition, the dye was found to inhibit hOCT1- and hOCT2-mediated uptake of tetraethylammonium (TEA), a model substrate for both hOCT1 and hOCT2; rhodamine 123 appeared nevertheless to be a more potent inhibitor of hOCT1-mediated TEA transport (IC(50) = 0.37 μm) than of that mediated by hOCT2 (IC(50 ) = 61.5 μm). Taken together, these data demonstrate that rhodamine 123 is a high-affinity substrate for both hOCT1 and hOCT2. This dye may be therefore useful for fluorimetrically investigating cellular hOCT1 or hOCT2 activity, knowing, however, that other factors potentially contributing to cellular accumulation of rhodamine 123, including mitochondrial membrane potential or expression of the efflux transporter P-glycoprotein, have also to be considered.</description>
<date>2012-07-24</date>
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