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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Transport of biogenic amine neurotransmitters at the mouse blood–retina and blood–brain barriers by uptake1 and uptake2</title><author><name sortKey="Andre, Pascal" sort="Andre, Pascal" uniqKey="Andre P" first="Pascal" last="André">Pascal André</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Saubamea, Bruno" sort="Saubamea, Bruno" uniqKey="Saubamea B" first="Bruno" last="Saubaméa">Bruno Saubaméa</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cochois Guegan, Veronique" sort="Cochois Guegan, Veronique" uniqKey="Cochois Guegan V" first="Véronique" last="Cochois-Guégan">Véronique Cochois-Guégan</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Marie Claire, Cynthia" sort="Marie Claire, Cynthia" uniqKey="Marie Claire C" first="Cynthia" last="Marie-Claire">Cynthia Marie-Claire</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cattelotte, Julie" sort="Cattelotte, Julie" uniqKey="Cattelotte J" first="Julie" last="Cattelotte">Julie Cattelotte</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Smirnova, Maria" sort="Smirnova, Maria" uniqKey="Smirnova M" first="Maria" last="Smirnova">Maria Smirnova</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Schinkel, Alfred H" sort="Schinkel, Alfred H" uniqKey="Schinkel A" first="Alfred H" last="Schinkel">Alfred H. Schinkel</name><affiliation><nlm:aff id="aff2"><institution>Division of Molecular Biology, The Netherlands Cancer Institute</institution>, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Scherrmann, Jean Michel" sort="Scherrmann, Jean Michel" uniqKey="Scherrmann J" first="Jean-Michel" last="Scherrmann">Jean-Michel Scherrmann</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Assistance Publique des Hôpitaux de Paris, AP-HP</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cisternino, Salvatore" sort="Cisternino, Salvatore" uniqKey="Cisternino S" first="Salvatore" last="Cisternino">Salvatore Cisternino</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Assistance Publique des Hôpitaux de Paris, AP-HP</institution>, Paris,<country>France</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22850405</idno><idno type="pmc">3493996</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493996</idno><idno type="RBID">PMC:3493996</idno><idno type="doi">10.1038/jcbfm.2012.109</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000005</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000005</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transport of biogenic amine neurotransmitters at the mouse blood–retina and blood–brain barriers by uptake1 and uptake2</title><author><name sortKey="Andre, Pascal" sort="Andre, Pascal" uniqKey="Andre P" first="Pascal" last="André">Pascal André</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Saubamea, Bruno" sort="Saubamea, Bruno" uniqKey="Saubamea B" first="Bruno" last="Saubaméa">Bruno Saubaméa</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cochois Guegan, Veronique" sort="Cochois Guegan, Veronique" uniqKey="Cochois Guegan V" first="Véronique" last="Cochois-Guégan">Véronique Cochois-Guégan</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Marie Claire, Cynthia" sort="Marie Claire, Cynthia" uniqKey="Marie Claire C" first="Cynthia" last="Marie-Claire">Cynthia Marie-Claire</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cattelotte, Julie" sort="Cattelotte, Julie" uniqKey="Cattelotte J" first="Julie" last="Cattelotte">Julie Cattelotte</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Smirnova, Maria" sort="Smirnova, Maria" uniqKey="Smirnova M" first="Maria" last="Smirnova">Maria Smirnova</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Schinkel, Alfred H" sort="Schinkel, Alfred H" uniqKey="Schinkel A" first="Alfred H" last="Schinkel">Alfred H. Schinkel</name><affiliation><nlm:aff id="aff2"><institution>Division of Molecular Biology, The Netherlands Cancer Institute</institution>, Amsterdam,<country>The Netherlands</country></nlm:aff></affiliation></author><author><name sortKey="Scherrmann, Jean Michel" sort="Scherrmann, Jean Michel" uniqKey="Scherrmann J" first="Jean-Michel" last="Scherrmann">Jean-Michel Scherrmann</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Assistance Publique des Hôpitaux de Paris, AP-HP</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Cisternino, Salvatore" sort="Cisternino, Salvatore" uniqKey="Cisternino S" first="Salvatore" last="Cisternino">Salvatore Cisternino</name><affiliation><nlm:aff id="aff1"><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Assistance Publique des Hôpitaux de Paris, AP-HP</institution>, Paris,<country>France</country></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Cerebral Blood Flow & Metabolism</title><idno type="ISSN">0271-678X</idno><idno type="eISSN">1559-7016</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Uptake1 and uptake2 transporters are involved in the extracellular clearance of biogenic amine neurotransmitters at synaptic clefts. We looked for them at the blood–brain barrier (BBB) and blood–retina barriers (BRB), where they could be involved in regulating the neurotransmitter concentration and modulate/terminate receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1-3/Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in the transport of xenobiotics. We used <italic>in situ</italic> carotid perfusion of prototypic substrates like [<sup>3</sup>H]-1-methyl-4-phenylpyridinium ([<sup>3</sup>H]-MPP<sup>+</sup>), [<sup>3</sup>H]-histamine, [<sup>3</sup>H]-serotonin, and [<sup>3</sup>H]-dopamine, changes in ionic composition and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB and BRB. We showed that uptake1 and uptake2 are involved in the transport of [<sup>3</sup>H]-dopamine and [<sup>3</sup>H]-MPP<sup>+</sup> at the blood luminal BRB, but not at the BBB. These functional studies, together with quantitative RT-PCR and confocal imaging, suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4), uptake2, and Mate1 on both the luminal and abluminal sides. However, we found evidence for functional Net and Oct1 transporters at the luminal BRB. These heterogeneous transport properties of the brain and retina NVUs suggest that the BBB helps protect the brain against biogenic amine neurotransmitters in the plasma while the BRB has more of a metabolic/endocrine role.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Cereb Blood Flow Metab</journal-id><journal-id journal-id-type="iso-abbrev">J. Cereb. Blood Flow Metab</journal-id><journal-title-group><journal-title>Journal of Cerebral Blood Flow & Metabolism</journal-title></journal-title-group><issn pub-type="ppub">0271-678X</issn><issn pub-type="epub">1559-7016</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22850405</article-id><article-id pub-id-type="pmc">3493996</article-id><article-id pub-id-type="pii">jcbfm2012109</article-id><article-id pub-id-type="doi">10.1038/jcbfm.2012.109</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Transport of biogenic amine neurotransmitters at the mouse blood–retina and blood–brain barriers by uptake1 and uptake2</article-title><alt-title alt-title-type="running">Biogenic amine carriers at the retina and brain barriers</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>André</surname><given-names>Pascal</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Saubaméa</surname><given-names>Bruno</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cochois-Guégan</surname><given-names>Véronique</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Marie-Claire</surname><given-names>Cynthia</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cattelotte</surname><given-names>Julie</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Smirnova</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Schinkel</surname><given-names>Alfred H</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Scherrmann</surname><given-names>Jean-Michel</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cisternino</surname><given-names>Salvatore</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Université Paris Diderot, Faculté de Pharmacie</institution>, Paris,<country>France</country></aff><aff id="aff2"><label>2</label><institution>Division of Molecular Biology, The Netherlands Cancer Institute</institution>, Amsterdam,<country>The Netherlands</country></aff><aff id="aff3"><label>3</label><institution>Assistance Publique des Hôpitaux de Paris, AP-HP</institution>, Paris,<country>France</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>INSERM U705, CNRS UMR 8206, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques</institution>, Pharmacocinétique, 4, Avenue de l'Observatoire, 75006 Paris, <country>France</country>. E-mail: <email>salvatore.cisternino@jvr.aphp.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>01</day><month>08</month><year>2012</year></pub-date><volume>32</volume><issue>11</issue><fpage>1989</fpage><lpage>2001</lpage><history><date date-type="received"><day>11</day><month>03</month><year>2012</year></date><date date-type="rev-recd"><day>01</day><month>07</month><year>2012</year></date><date date-type="accepted"><day>04</day><month>07</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012 International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-holder></permissions><abstract><p>Uptake1 and uptake2 transporters are involved in the extracellular clearance of biogenic amine neurotransmitters at synaptic clefts. We looked for them at the blood–brain barrier (BBB) and blood–retina barriers (BRB), where they could be involved in regulating the neurotransmitter concentration and modulate/terminate receptor-mediated effects within the neurovascular unit (NVU). Uptake2 (Oct1-3/Slc22a1-3, Pmat/Slc29a4) and Mate1/Slc47a1 transporters are also involved in the transport of xenobiotics. We used <italic>in situ</italic> carotid perfusion of prototypic substrates like [<sup>3</sup>H]-1-methyl-4-phenylpyridinium ([<sup>3</sup>H]-MPP<sup>+</sup>), [<sup>3</sup>H]-histamine, [<sup>3</sup>H]-serotonin, and [<sup>3</sup>H]-dopamine, changes in ionic composition and genetic deletion of Oct1-3 carriers to detect uptake1 and uptake2 at the BBB and BRB. We showed that uptake1 and uptake2 are involved in the transport of [<sup>3</sup>H]-dopamine and [<sup>3</sup>H]-MPP<sup>+</sup> at the blood luminal BRB, but not at the BBB. These functional studies, together with quantitative RT-PCR and confocal imaging, suggest that the mouse BBB lacks uptake1 (Net/Slc6a2, Dat/Slc6a3, Sert/Slc6a4), uptake2, and Mate1 on both the luminal and abluminal sides. However, we found evidence for functional Net and Oct1 transporters at the luminal BRB. These heterogeneous transport properties of the brain and retina NVUs suggest that the BBB helps protect the brain against biogenic amine neurotransmitters in the plasma while the BRB has more of a metabolic/endocrine role.</p></abstract><kwd-group><kwd>blood–brain barrier</kwd><kwd>blood–retina barrier</kwd><kwd>dopamine</kwd><kwd>neurovascular unit</kwd><kwd>organic cation transporters</kwd><kwd>uptake transporters</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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