How animal toxins contribute to explore the role of ASIC channels in pain
| Autor: | Diochot, S, Verkest, C, Salinas, M, Piquet, E, Friend, V, Dauvois, M, Alloui, A, Eschalier, A, Mourier, G, Kessler, P, Lanteri-Minet, M, Servent, D, Deval, E, Lingueglia, E., Baron, Anne, Iii, A, Lanteriminet, M, Servent I V, D |
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| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | FEBS OPEN BIO FEBS OPEN BIO, Jul 2021, Ljubljana, Slovenia |
| Popis: | International audience; AcidSensing Ion Channels (ASICs) form a class of neuronal excitatory cation channels gated by extracellular protons. We have isolated several peptide toxins from seaanemone, spider and snake venoms which allowed to successfully explore the role of these channels in physiopathological processes such as pain. Mambalgin (Mamb1), was used to reveal the role of subtypes of ASIC channels in pain, including inflammatory and neuropathic pain. It acts as a potent and specific inhibitor of ASIC1acontaining channels, which are the major channel subtypes expressed in the central nervous system, and of peripheral ASIC1bcontaining channels that are specific of sensory neurons. Mamb1 shows potent analgesic effects on thermal and mechanical nociception upon different route of injection in experimental animal models of inflammatory and neuropathic pain. The effects can be as strong as morphine but involve opioidindependent pathways, without producing apparent toxicity. Mamb1 acts as a gatingmodifier that binds to the extracellular domain of the channel to block ASICs by a pH sensortrapping mechanism. We recently used this peptide to explore the involvement of the ASIC1 in a rodent model of acute and chronic migraine induced by systemic injections of isosorbide dinitrate (ISDN), a therapeutically used nitric oxide donor known to produce headache as sideeffect in humans. We studied the effects of systemic injections of Mamb1 on cutaneous allodynia, by testing cephalic and extracephalic mechanical sensitivity. A single ISDN injection induced migrainelike acute symptoms, whereas one daily ISDN injections during four days induced chronic effects. Intravenous injection of Mamb1 or amiloride, inhibited both the acute and the chronic mechanical allodynia. These data using a venom derived, peptide specific inhibitor support the involvement of central and peripheral ASIC1containing channels in pain and highlight the therapeutic potential of blocking these channels |
| Databáze: | OpenAIRE |
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