Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a
Identifieur interne : 000621 ( Main/Exploration ); précédent : 000620; suivant : 000622Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a
Auteurs : Jennifer R. Deuis [Australie] ; Zoltan Dekan [Australie] ; Joshua S. Wingerd [Australie] ; Jennifer J. Smith [Australie] ; Nehan R. Munasinghe [Australie] ; Rebecca F. Bhola [Australie] ; Wendy L. Imlach [Australie] ; Volker Herzig [Australie] ; David A. Armstrong [Australie] ; K. Johan Rosengren [Australie] ; Frank Bosmans [États-Unis] ; Stephen G. Waxman [États-Unis] ; Sulayman D. Dib-Hajj [États-Unis] ; Pierre Escoubas [France] ; Michael S. Minett [Royaume-Uni] ; Macdonald J. Christie [Australie] ; Glenn F. King [Australie] ; Paul F. Alewood [Australie] ; Richard J. Lewis [Australie] ; John N. Wood [Royaume-Uni] ; Irina Vetter [Australie]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula
Url:
DOI: 10.1038/srep40883
PubMed: 28106092
PubMed Central: 5247677
Affiliations:
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Deuis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dekan, Zoltan" sort="Dekan, Zoltan" uniqKey="Dekan Z" first="Zoltan" last="Dekan">Zoltan Dekan</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wingerd, Joshua S" sort="Wingerd, Joshua S" uniqKey="Wingerd J" first="Joshua S." last="Wingerd">Joshua S. Wingerd</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith, Jennifer J" sort="Smith, Jennifer J" uniqKey="Smith J" first="Jennifer J." last="Smith">Jennifer J. Smith</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Munasinghe, Nehan R" sort="Munasinghe, Nehan R" uniqKey="Munasinghe N" first="Nehan R." last="Munasinghe">Nehan R. Munasinghe</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bhola, Rebecca F" sort="Bhola, Rebecca F" uniqKey="Bhola R" first="Rebecca F." last="Bhola">Rebecca F. Bhola</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Imlach, Wendy L" sort="Imlach, Wendy L" uniqKey="Imlach W" first="Wendy L." last="Imlach">Wendy L. 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Minett</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Christie, Macdonald J" sort="Christie, Macdonald J" uniqKey="Christie M" first="Macdonald J." last="Christie">Macdonald J. Christie</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Discipline of Pharmacology, School of Medical Sciences, The University of Sydney, Sydney</institution>, New South Wales, 2006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="King, Glenn F" sort="King, Glenn F" uniqKey="King G" first="Glenn F." last="King">Glenn F. 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Alewood</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Richard J" sort="Lewis, Richard J" uniqKey="Lewis R" first="Richard J." last="Lewis">Richard J. Lewis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wood, John N" sort="Wood, John N" uniqKey="Wood J" first="John N." last="Wood">John N. Wood</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London</institution>, London WC1E 6BT,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>IMB Centre for Pain Research, Institute for Molecular Bioscience, 306 Carmody Rd (Building 80), The University of Queensland, St Lucia</institution>, Queensland, 4072,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a8"><institution>School of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence, 20 Cornwall St, Woolloongabba</institution>, Queensland, 4102,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human genetic studies have implicated the voltage-gated sodium channel Na<sub>V</sub>1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula <italic>Pamphobeteus nigricolor,</italic> potently inhibits Na<sub>V</sub>1.7 (IC<sub>50</sub> 0.9 nM) with at least 40–1000-fold selectivity over all other Na<sub>V</sub> subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by Na<sub>V</sub>1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically. A broad lack of analgesic activity was also found for the selective Na<sub>V</sub>1.7 inhibitors PF-04856264 and phlotoxin 1. However, when administered with subtherapeutic doses of opioids or the enkephalinase inhibitor thiorphan, these subtype-selective Na<sub>V</sub>1.7 inhibitors produced profound analgesia. 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Yaksh</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>États-Unis</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Deuis, Jennifer R" sort="Deuis, Jennifer R" uniqKey="Deuis J" first="Jennifer R." last="Deuis">Jennifer R. Deuis</name></noRegion><name sortKey="Alewood, Paul F" sort="Alewood, Paul F" uniqKey="Alewood P" first="Paul F." last="Alewood">Paul F. Alewood</name><name sortKey="Armstrong, David A" sort="Armstrong, David A" uniqKey="Armstrong D" first="David A." last="Armstrong">David A. Armstrong</name><name sortKey="Bhola, Rebecca F" sort="Bhola, Rebecca F" uniqKey="Bhola R" first="Rebecca F." last="Bhola">Rebecca F. Bhola</name><name sortKey="Christie, Macdonald J" sort="Christie, Macdonald J" uniqKey="Christie M" first="Macdonald J." last="Christie">Macdonald J. Christie</name><name sortKey="Dekan, Zoltan" sort="Dekan, Zoltan" uniqKey="Dekan Z" first="Zoltan" last="Dekan">Zoltan Dekan</name><name sortKey="Herzig, Volker" sort="Herzig, Volker" uniqKey="Herzig V" first="Volker" last="Herzig">Volker Herzig</name><name sortKey="Imlach, Wendy L" sort="Imlach, Wendy L" uniqKey="Imlach W" first="Wendy L." last="Imlach">Wendy L. Imlach</name><name sortKey="King, Glenn F" sort="King, Glenn F" uniqKey="King G" first="Glenn F." last="King">Glenn F. King</name><name sortKey="Lewis, Richard J" sort="Lewis, Richard J" uniqKey="Lewis R" first="Richard J." last="Lewis">Richard J. Lewis</name><name sortKey="Munasinghe, Nehan R" sort="Munasinghe, Nehan R" uniqKey="Munasinghe N" first="Nehan R." last="Munasinghe">Nehan R. Munasinghe</name><name sortKey="Rosengren, K Johan" sort="Rosengren, K Johan" uniqKey="Rosengren K" first="K. Johan" last="Rosengren">K. Johan Rosengren</name><name sortKey="Smith, Jennifer J" sort="Smith, Jennifer J" uniqKey="Smith J" first="Jennifer J." last="Smith">Jennifer J. Smith</name><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name><name sortKey="Wingerd, Joshua S" sort="Wingerd, Joshua S" uniqKey="Wingerd J" first="Joshua S." last="Wingerd">Joshua S. Wingerd</name></country><country name="États-Unis"><noRegion><name sortKey="Bosmans, Frank" sort="Bosmans, Frank" uniqKey="Bosmans F" first="Frank" last="Bosmans">Frank Bosmans</name></noRegion><name sortKey="Dib Hajj, Sulayman D" sort="Dib Hajj, Sulayman D" uniqKey="Dib Hajj S" first="Sulayman D." last="Dib-Hajj">Sulayman D. Dib-Hajj</name><name sortKey="Waxman, Stephen G" sort="Waxman, Stephen G" uniqKey="Waxman S" first="Stephen G." last="Waxman">Stephen G. Waxman</name></country><country name="France"><noRegion><name sortKey="Escoubas, Pierre" sort="Escoubas, Pierre" uniqKey="Escoubas P" first="Pierre" last="Escoubas">Pierre Escoubas</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Minett, Michael S" sort="Minett, Michael S" uniqKey="Minett M" first="Michael S." last="Minett">Michael S. Minett</name></noRegion><name sortKey="Wood, John N" sort="Wood, John N" uniqKey="Wood J" first="John N." last="Wood">John N. Wood</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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