Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins.
Identifieur interne : 002D44 ( Ncbi/Checkpoint ); précédent : 002D43; suivant : 002D45Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins.
Auteurs : Raphaele Le Garrec [France] ; Killian L'Herondelle [France] ; Christelle Le Gall-Ianotto [France] ; Nicolas Lebonvallet [France] ; Raphael Leschiera [France] ; Virginie Buhe [France] ; Matthieu Talagas [France] ; Irina Vetter [Australie] ; Richard J. Lewis [Australie] ; Laurent Misery [France]Source :
- Toxicon : official journal of the International Society on Toxinology [ 1879-3150 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Calcium (métabolisme), Cellules réceptrices sensorielles (), Cellules réceptrices sensorielles (cytologie), Ciguatera, Ciguatoxines (), Ciguatoxines (pharmacologie), Humains, Immunohistochimie, Kératinocytes (), Kératinocytes (cytologie), Modèles biologiques, Neuropeptide CGRP (métabolisme), Neuropeptides (métabolisme), Rats, Techniques de coculture.
- MESH :
- cytologie : Cellules réceptrices sensorielles, Kératinocytes.
- métabolisme : Calcium, Neuropeptide CGRP, Neuropeptides.
- pharmacologie : Ciguatoxines.
- Animaux, Cellules réceptrices sensorielles, Ciguatera, Ciguatoxines, Humains, Immunohistochimie, Kératinocytes, Modèles biologiques, Rats, Techniques de coculture.
English descriptors
- KwdEn :
- Animals, Calcitonin Gene-Related Peptide (metabolism), Calcium (metabolism), Ciguatera Poisoning, Ciguatoxins (chemistry), Ciguatoxins (pharmacology), Coculture Techniques, Humans, Immunohistochemistry, Keratinocytes (cytology), Keratinocytes (drug effects), Models, Biological, Neuropeptides (metabolism), Rats, Sensory Receptor Cells (cytology), Sensory Receptor Cells (drug effects).
- MESH :
- chemical , chemistry : Ciguatoxins.
- chemical , metabolism : Calcitonin Gene-Related Peptide, Calcium, Neuropeptides.
- chemical , pharmacology : Ciguatoxins.
- cytology : Keratinocytes, Sensory Receptor Cells.
- drug effects : Keratinocytes, Sensory Receptor Cells.
- Animals, Ciguatera Poisoning, Coculture Techniques, Humans, Immunohistochemistry, Models, Biological, Rats.
Abstract
Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning.
DOI: 10.1016/j.toxicon.2015.11.004
PubMed: 26562445
Affiliations:
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<term>Calcitonin Gene-Related Peptide (metabolism)</term>
<term>Calcium (metabolism)</term>
<term>Ciguatera Poisoning</term>
<term>Ciguatoxins (chemistry)</term>
<term>Ciguatoxins (pharmacology)</term>
<term>Coculture Techniques</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Keratinocytes (cytology)</term>
<term>Keratinocytes (drug effects)</term>
<term>Models, Biological</term>
<term>Neuropeptides (metabolism)</term>
<term>Rats</term>
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<term>Sensory Receptor Cells (drug effects)</term>
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<term>Calcium (métabolisme)</term>
<term>Cellules réceptrices sensorielles ()</term>
<term>Cellules réceptrices sensorielles (cytologie)</term>
<term>Ciguatera</term>
<term>Ciguatoxines ()</term>
<term>Ciguatoxines (pharmacologie)</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Kératinocytes ()</term>
<term>Kératinocytes (cytologie)</term>
<term>Modèles biologiques</term>
<term>Neuropeptide CGRP (métabolisme)</term>
<term>Neuropeptides (métabolisme)</term>
<term>Rats</term>
<term>Techniques de coculture</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Ciguatoxins</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcitonin Gene-Related Peptide</term>
<term>Calcium</term>
<term>Neuropeptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Ciguatoxins</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules réceptrices sensorielles</term>
<term>Kératinocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Keratinocytes</term>
<term>Sensory Receptor Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Keratinocytes</term>
<term>Sensory Receptor Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calcium</term>
<term>Neuropeptide CGRP</term>
<term>Neuropeptides</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Ciguatoxines</term>
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<term>Ciguatera Poisoning</term>
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<term>Cellules réceptrices sensorielles</term>
<term>Ciguatera</term>
<term>Ciguatoxines</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Kératinocytes</term>
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<front><div type="abstract" xml:lang="en">Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning.</div>
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<name sortKey="L Herondelle, Killian" sort="L Herondelle, Killian" uniqKey="L Herondelle K" first="Killian" last="L'Herondelle">Killian L'Herondelle</name>
<name sortKey="Le Gall Ianotto, Christelle" sort="Le Gall Ianotto, Christelle" uniqKey="Le Gall Ianotto C" first="Christelle" last="Le Gall-Ianotto">Christelle Le Gall-Ianotto</name>
<name sortKey="Lebonvallet, Nicolas" sort="Lebonvallet, Nicolas" uniqKey="Lebonvallet N" first="Nicolas" last="Lebonvallet">Nicolas Lebonvallet</name>
<name sortKey="Leschiera, Raphael" sort="Leschiera, Raphael" uniqKey="Leschiera R" first="Raphael" last="Leschiera">Raphael Leschiera</name>
<name sortKey="Misery, Laurent" sort="Misery, Laurent" uniqKey="Misery L" first="Laurent" last="Misery">Laurent Misery</name>
<name sortKey="Talagas, Matthieu" sort="Talagas, Matthieu" uniqKey="Talagas M" first="Matthieu" last="Talagas">Matthieu Talagas</name>
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<country name="Australie"><noRegion><name sortKey="Vetter, Irina" sort="Vetter, Irina" uniqKey="Vetter I" first="Irina" last="Vetter">Irina Vetter</name>
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<name sortKey="Lewis, Richard J" sort="Lewis, Richard J" uniqKey="Lewis R" first="Richard J" last="Lewis">Richard J. Lewis</name>
</country>
</tree>
</affiliations>
</record>
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