Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi
Identifieur interne : 000E17 ( Main/Exploration ); précédent : 000E16; suivant : 000E18Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi
Auteurs : Silmara R. Sousa [Australie] ; Joshua S. Wingerd [Australie] ; Andreas Brust [Australie] ; Christopher Bladen [Canada] ; Lotten Ragnarsson [Australie] ; Volker Herzig [Australie] ; Jennifer R. Deuis [Australie] ; Sebastien Dutertre [France] ; Irina Vetter [Australie] ; Gerald W. Zamponi [Canada] ; Glenn F. King [Australie] ; Paul F. Alewood [Australie] ; Richard J. Lewis [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Descripteurs français
- KwdFr :
- Analgésiques (), Analgésiques (pharmacologie), Animaux, Araignées (), Canal sodique voltage-dépendant NAV1.1 (métabolisme), Canal sodique voltage-dépendant NAV1.7 (métabolisme), Canaux calciques de type N (métabolisme), Fluorimétrie, Humains, Peptides (), Peptides (pharmacologie), Rats, Sites de fixation (), Souris, Venins d'araignée (), Électrophysiologie.
- MESH :
- métabolisme : Canal sodique voltage-dépendant NAV1.1, Canal sodique voltage-dépendant NAV1.7, Canaux calciques de type N.
- pharmacologie : Analgésiques, Peptides.
- Analgésiques, Animaux, Araignées, Fluorimétrie, Humains, Peptides, Rats, Sites de fixation, Souris, Venins d'araignée, Électrophysiologie.
English descriptors
- KwdEn :
- Analgesics (chemistry), Analgesics (pharmacology), Animals, Binding Sites (drug effects), Calcium Channels, N-Type (metabolism), Electrophysiology, Fluorometry, Humans, Mice, NAV1.1 Voltage-Gated Sodium Channel (metabolism), NAV1.7 Voltage-Gated Sodium Channel (metabolism), Peptides (chemistry), Peptides (pharmacology), Rats, Spider Venoms (chemistry), Spiders (chemistry).
- MESH :
- chemical , chemistry : Analgesics, Peptides, Spider Venoms.
- chemical , metabolism : Calcium Channels, N-Type, NAV1.1 Voltage-Gated Sodium Channel, NAV1.7 Voltage-Gated Sodium Channel.
- chemical , pharmacology : Analgesics, Peptides.
- chemistry : Spiders.
- drug effects : Binding Sites.
- Animals, Electrophysiology, Fluorometry, Humans, Mice, Rats.
Abstract
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider
Url:
DOI: 10.1371/journal.pone.0182848
PubMed: 28880874
PubMed Central: 5589098
Affiliations:
- Australie, Canada, France
- Alberta, Languedoc-Roussillon, Occitanie (région administrative)
- Calgary, Montpellier
- Université de Calgary
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 002993
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- to stream Pmc, to step Checkpoint: 000365
- to stream PubMed, to step Corpus: 000503
- to stream PubMed, to step Curation: 000501
- to stream PubMed, to step Checkpoint: 000501
- to stream Ncbi, to step Merge: 004E17
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- to stream Ncbi, to step Checkpoint: 004E17
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Analgesics (chemistry)</term>
<term>Analgesics (pharmacology)</term>
<term>Animals</term>
<term>Binding Sites (drug effects)</term>
<term>Calcium Channels, N-Type (metabolism)</term>
<term>Electrophysiology</term>
<term>Fluorometry</term>
<term>Humans</term>
<term>Mice</term>
<term>NAV1.1 Voltage-Gated Sodium Channel (metabolism)</term>
<term>NAV1.7 Voltage-Gated Sodium Channel (metabolism)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (pharmacology)</term>
<term>Rats</term>
<term>Spider Venoms (chemistry)</term>
<term>Spiders (chemistry)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Analgésiques ()</term>
<term>Analgésiques (pharmacologie)</term>
<term>Animaux</term>
<term>Araignées ()</term>
<term>Canal sodique voltage-dépendant NAV1.1 (métabolisme)</term>
<term>Canal sodique voltage-dépendant NAV1.7 (métabolisme)</term>
<term>Canaux calciques de type N (métabolisme)</term>
<term>Fluorimétrie</term>
<term>Humains</term>
<term>Peptides ()</term>
<term>Peptides (pharmacologie)</term>
<term>Rats</term>
<term>Sites de fixation ()</term>
<term>Souris</term>
<term>Venins d'araignée ()</term>
<term>Électrophysiologie</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Analgesics</term>
<term>Peptides</term>
<term>Spider Venoms</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium Channels, N-Type</term>
<term>NAV1.1 Voltage-Gated Sodium Channel</term>
<term>NAV1.7 Voltage-Gated Sodium Channel</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Analgesics</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Spiders</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Binding Sites</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Canal sodique voltage-dépendant NAV1.1</term>
<term>Canal sodique voltage-dépendant NAV1.7</term>
<term>Canaux calciques de type N</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Analgésiques</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Electrophysiology</term>
<term>Fluorometry</term>
<term>Humans</term>
<term>Mice</term>
<term>Rats</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analgésiques</term>
<term>Animaux</term>
<term>Araignées</term>
<term>Fluorimétrie</term>
<term>Humains</term>
<term>Peptides</term>
<term>Rats</term>
<term>Sites de fixation</term>
<term>Souris</term>
<term>Venins d'araignée</term>
<term>Électrophysiologie</term>
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<front><div type="abstract" xml:lang="en"><p>Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider <italic>Ceratogyrus darlingi</italic>
. Cd1a reversibly paralysed sheep blowflies (PD<sub>50</sub>
of 1318 pmol/g) and inhibited human Ca<sub>v</sub>
2.2 (IC<sub>50</sub>
2.6 μM) but not Ca<sub>v</sub>
1.3 or Ca<sub>v</sub>
3.1 (IC<sub>50</sub>
> 30 μM) in fluorimetric assays. In patch-clamp electrophysiological assays Cd1a inhibited rat Ca<sub>v</sub>
2.2 with similar potency (IC<sub>50</sub>
3 μM) without influencing the voltage dependence of Ca<sub>v</sub>
2.2 activation gating, suggesting that Cd1a doesn’t act on Ca<sub>v</sub>
2.2 as a classical gating modifier toxin. The Cd1a binding site on Ca<sub>v</sub>
2.2 did not overlap with that of the pore blocker ω-conotoxin GVIA, but its activity at Ca<sub>v</sub>
2.2-mutant indicated that Cd1a shares some molecular determinants with GVIA and MVIIA, localized near the pore region. Cd1a also inhibited human Na<sub>v</sub>
1.1–1.2 and Na<sub>v</sub>
1.7–1.8 (IC<sub>50</sub>
0.1–6.9 μM) but not Na<sub>v</sub>
1.3–1.6 (IC<sub>50</sub>
> 30 μM) in fluorimetric assays. In patch-clamp assays, Cd1a strongly inhibited human Na<sub>v</sub>
1.7 (IC<sub>50</sub>
16 nM) and produced a 29 mV depolarising shift in Na<sub>v</sub>
1.7 voltage dependence of activation. Cd1a (400 pmol) fully reversed Na<sub>v</sub>
1.7-evoked pain behaviours in mice without producing side effects. In conclusion, Cd1a inhibited two anti-nociceptive targets, appearing to interfere with Ca<sub>v</sub>
2.2 inactivation gating, associated with the Ca<sub>v</sub>
2.2 α-subunit pore, while altering the activation gating of Na<sub>v</sub>
1.7. Cd1a was inactive at some of the Na<sub>v</sub>
and Ca<sub>v</sub>
channels expressed in skeletal and cardiac muscles and nodes of Ranvier, apparently contributing to the lack of side effects at efficacious doses, and suggesting potential as a lead for development of peripheral pain treatments.</p>
</div>
</front>
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</author>
<author><name sortKey="Zhang, Jf" uniqKey="Zhang J">JF Zhang</name>
</author>
<author><name sortKey="Horne, Wa" uniqKey="Horne W">WA Horne</name>
</author>
<author><name sortKey="Tsien, Rw" uniqKey="Tsien R">RW Tsien</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Feng, Zp" uniqKey="Feng Z">ZP Feng</name>
</author>
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<author><name sortKey="Snutch, Tp" uniqKey="Snutch T">TP Snutch</name>
</author>
<author><name sortKey="Zamponi, Gw" uniqKey="Zamponi G">GW Zamponi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sokolov, S" uniqKey="Sokolov S">S Sokolov</name>
</author>
<author><name sortKey="Kraus, Rl" uniqKey="Kraus R">RL Kraus</name>
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<author><name sortKey="Scheuer, T" uniqKey="Scheuer T">T Scheuer</name>
</author>
<author><name sortKey="Catterall, Wa" uniqKey="Catterall W">WA Catterall</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maertens, C" uniqKey="Maertens C">C Maertens</name>
</author>
<author><name sortKey="Cuypers, E" uniqKey="Cuypers E">E Cuypers</name>
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<author><name sortKey="Tytgat, J" uniqKey="Tytgat J">J Tytgat</name>
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</analytic>
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</author>
<author><name sortKey="King, Gf" uniqKey="King G">GF King</name>
</author>
</analytic>
</biblStruct>
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<author><name sortKey="Jarvis, Se" uniqKey="Jarvis S">SE Jarvis</name>
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<author><name sortKey="Zamponi, Gw" uniqKey="Zamponi G">GW Zamponi</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mathes, C" uniqKey="Mathes C">C Mathes</name>
</author>
<author><name sortKey="Friis, S" uniqKey="Friis S">S Friis</name>
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<author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name>
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</analytic>
</biblStruct>
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</author>
<author><name sortKey="Roncarati, R" uniqKey="Roncarati R">R Roncarati</name>
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<author><name sortKey="Dunlop, J" uniqKey="Dunlop J">J Dunlop</name>
</author>
<author><name sortKey="Peri, R" uniqKey="Peri R">R Peri</name>
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</analytic>
</biblStruct>
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</author>
<author><name sortKey="Williams, Bs" uniqKey="Williams B">BS Williams</name>
</author>
<author><name sortKey="Priest, Bt" uniqKey="Priest B">BT Priest</name>
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</author>
<author><name sortKey="Dick, Ie" uniqKey="Dick I">IE Dick</name>
</author>
<author><name sortKey="Warren, Va" uniqKey="Warren V">VA Warren</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="King, Gf" uniqKey="King G">GF King</name>
</author>
<author><name sortKey="Gentz, Mc" uniqKey="Gentz M">MC Gentz</name>
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</biblStruct>
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<author><name sortKey="Ragsdale, Ds" uniqKey="Ragsdale D">DS Ragsdale</name>
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<author><name sortKey="Catterall, Wa" uniqKey="Catterall W">WA Catterall</name>
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<author><name sortKey="Blumenthal, K" uniqKey="Blumenthal K">K Blumenthal</name>
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</biblStruct>
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<author><name sortKey="Alewood, Pf" uniqKey="Alewood P">PF Alewood</name>
</author>
</analytic>
</biblStruct>
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</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>France</li>
</country>
<region><li>Alberta</li>
<li>Languedoc-Roussillon</li>
<li>Occitanie (région administrative)</li>
</region>
<settlement><li>Calgary</li>
<li>Montpellier</li>
</settlement>
<orgName><li>Université de Calgary</li>
</orgName>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Sousa, Silmara R" sort="Sousa, Silmara R" uniqKey="Sousa S" first="Silmara R." last="Sousa">Silmara R. Sousa</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="Brust, Andreas" sort="Brust, Andreas" uniqKey="Brust A" first="Andreas" last="Brust">Andreas Brust</name>
<name sortKey="Deuis, Jennifer R" sort="Deuis, Jennifer R" uniqKey="Deuis J" first="Jennifer R." last="Deuis">Jennifer R. Deuis</name>
<name sortKey="Herzig, Volker" sort="Herzig, Volker" uniqKey="Herzig V" first="Volker" last="Herzig">Volker Herzig</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="Ragnarsson, Lotten" sort="Ragnarsson, Lotten" uniqKey="Ragnarsson L" first="Lotten" last="Ragnarsson">Lotten Ragnarsson</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="Canada"><region name="Alberta"><name sortKey="Bladen, Christopher" sort="Bladen, Christopher" uniqKey="Bladen C" first="Christopher" last="Bladen">Christopher Bladen</name>
</region>
<name sortKey="Zamponi, Gerald W" sort="Zamponi, Gerald W" uniqKey="Zamponi G" first="Gerald W." last="Zamponi">Gerald W. Zamponi</name>
</country>
<country name="France"><region name="Occitanie (région administrative)"><name sortKey="Dutertre, Sebastien" sort="Dutertre, Sebastien" uniqKey="Dutertre S" first="Sebastien" last="Dutertre">Sebastien Dutertre</name>
</region>
</country>
</tree>
</affiliations>
</record>
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