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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">μ-Opioid receptor 6-transmembrane isoform: a potential therapeutic target for new effective opioids</title><author><name sortKey="Convertino, Marino" sort="Convertino, Marino" uniqKey="Convertino M" first="Marino" last="Convertino">Marino Convertino</name><affiliation><nlm:aff id="A1"> Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Samoshkin, Alexander" sort="Samoshkin, Alexander" uniqKey="Samoshkin A" first="Alexander" last="Samoshkin">Alexander Samoshkin</name><affiliation><nlm:aff id="A2"> The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1.</nlm:aff></affiliation></author><author><name sortKey="Gauthier, Josee" sort="Gauthier, Josee" uniqKey="Gauthier J" first="Josee" last="Gauthier">Josee Gauthier</name><affiliation><nlm:aff id="A3"> Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Gold, Michael S" sort="Gold, Michael S" uniqKey="Gold M" first="Michael S." last="Gold">Michael S. Gold</name><affiliation><nlm:aff id="A4"> Department of Anesthesiology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA, USA 15213.</nlm:aff></affiliation></author><author><name sortKey="Maixner, William" sort="Maixner, William" uniqKey="Maixner W" first="William" last="Maixner">William Maixner</name><affiliation><nlm:aff id="A3"> Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Dokholyan, Nikolay V" sort="Dokholyan, Nikolay V" uniqKey="Dokholyan N" first="Nikolay V." last="Dokholyan">Nikolay V. Dokholyan</name><affiliation><nlm:aff id="A1"> Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Diatchenko, Luda" sort="Diatchenko, Luda" uniqKey="Diatchenko L" first="Luda" last="Diatchenko">Luda Diatchenko</name><affiliation><nlm:aff id="A2"> The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25485963</idno><idno type="pmc">4646084</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646084</idno><idno type="RBID">PMC:4646084</idno><idno type="doi">10.1016/j.pnpbp.2014.11.009</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001516</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001516</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">μ-Opioid receptor 6-transmembrane isoform: a potential therapeutic target for new effective opioids</title><author><name sortKey="Convertino, Marino" sort="Convertino, Marino" uniqKey="Convertino M" first="Marino" last="Convertino">Marino Convertino</name><affiliation><nlm:aff id="A1"> Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Samoshkin, Alexander" sort="Samoshkin, Alexander" uniqKey="Samoshkin A" first="Alexander" last="Samoshkin">Alexander Samoshkin</name><affiliation><nlm:aff id="A2"> The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1.</nlm:aff></affiliation></author><author><name sortKey="Gauthier, Josee" sort="Gauthier, Josee" uniqKey="Gauthier J" first="Josee" last="Gauthier">Josee Gauthier</name><affiliation><nlm:aff id="A3"> Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Gold, Michael S" sort="Gold, Michael S" uniqKey="Gold M" first="Michael S." last="Gold">Michael S. Gold</name><affiliation><nlm:aff id="A4"> Department of Anesthesiology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA, USA 15213.</nlm:aff></affiliation></author><author><name sortKey="Maixner, William" sort="Maixner, William" uniqKey="Maixner W" first="William" last="Maixner">William Maixner</name><affiliation><nlm:aff id="A3"> Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Dokholyan, Nikolay V" sort="Dokholyan, Nikolay V" uniqKey="Dokholyan N" first="Nikolay V." last="Dokholyan">Nikolay V. Dokholyan</name><affiliation><nlm:aff id="A1"> Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599.</nlm:aff></affiliation></author><author><name sortKey="Diatchenko, Luda" sort="Diatchenko, Luda" uniqKey="Diatchenko L" first="Luda" last="Diatchenko">Luda Diatchenko</name><affiliation><nlm:aff id="A2"> The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1.</nlm:aff></affiliation></author></analytic><series><title level="j">Progress in neuro-psychopharmacology & biological psychiatry</title><idno type="ISSN">0278-5846</idno><idno type="eISSN">1878-4216</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-perspective, we review the recently identified, functional MOR isoform subclass, which consists of six transmembrane helices (6TM) and may play an important role in MOR signaling. There is evidence that 6TM MOR signals through very different cellular pathways and may mediate excitatory cellular effects rather than the classic inhibitory effects produced by the stimulation of the major (7TM) isoform. Therefore, the development of 6TM and 7TM MOR selective compounds represent a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.</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>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8211617</journal-id><journal-id journal-id-type="pubmed-jr-id">6714</journal-id><journal-id journal-id-type="nlm-ta">Prog Neuropsychopharmacol Biol Psychiatry</journal-id><journal-id journal-id-type="iso-abbrev">Prog. Neuropsychopharmacol. Biol. Psychiatry</journal-id><journal-title-group><journal-title>Progress in neuro-psychopharmacology & biological psychiatry</journal-title></journal-title-group><issn pub-type="ppub">0278-5846</issn><issn pub-type="epub">1878-4216</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25485963</article-id><article-id pub-id-type="pmc">4646084</article-id><article-id pub-id-type="doi">10.1016/j.pnpbp.2014.11.009</article-id><article-id pub-id-type="manuscript">NIHMS647539</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>μ-Opioid receptor 6-transmembrane isoform: a potential therapeutic target for new effective opioids</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Convertino</surname><given-names>Marino</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Samoshkin</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Gauthier</surname><given-names>Josee</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Gold</surname><given-names>Michael S.</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Maixner</surname><given-names>William</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib><contrib contrib-type="author"><name><surname>Dokholyan</surname><given-names>Nikolay V.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib><contrib contrib-type="author"><name><surname>Diatchenko</surname><given-names>Luda</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label> Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599.</aff><aff id="A2"><label>2</label> The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1.</aff><aff id="A3"><label>3</label> Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599.</aff><aff id="A4"><label>4</label> Department of Anesthesiology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA, USA 15213.</aff><author-notes><corresp id="CR1"><label>*</label>CORRESPONDING AUTHORS: Dr. Luda Diatchenko, The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada, H3A 0G1, Phone: +1 514 398-2878, <email>luda.diatchenko@mcgill.ca</email>. Dr. William Maixner, Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC, USA, 27599, Phone: +1 919 537-3289, <email>bill_maixner@dentistry.unc.edu</email>. Dr. Nikolay V. Dokholyan, Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC, USA, 27599, Phone: +1 919 843-2513. <email>dokh@unc.edu</email>.</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>27</day><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>06</day><month>12</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>10</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>10</month><year>2016</year></pub-date><volume>62</volume><fpage>61</fpage><lpage>67</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.pnpbp.2014.11.009</pmc-comment>
<abstract id="Abs1"><p id="P1">The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-perspective, we review the recently identified, functional MOR isoform subclass, which consists of six transmembrane helices (6TM) and may play an important role in MOR signaling. There is evidence that 6TM MOR signals through very different cellular pathways and may mediate excitatory cellular effects rather than the classic inhibitory effects produced by the stimulation of the major (7TM) isoform. Therefore, the development of 6TM and 7TM MOR selective compounds represent a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.</p></abstract><abstract abstract-type="graphical" id="Abs2"><title>Graphical Abstract</title><p id="P2"><graphic xlink:href="nihms-647539-f0001.jpg" position="anchor" orientation="portrait"></graphic></p></abstract><kwd-group><kwd>Review</kwd><kwd>μ-opioid receptor</kwd><kwd>6TM MOR isoform</kwd><kwd>drug discovery</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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