The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity
| العنوان: | The marine phycotoxin gymnodimine targets muscular and neuronal nicotinic acetylcholine receptor subtypes with high affinity |
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| المؤلفون: | Riadh Marrouchi, Denis Servent, Gilles Ouanounou, Muriel Amar, Evelyne Benoit, Emmanuelle Girard, R. Kharrat, Jordi Molgó |
| المساهمون: | Laboratoire des Toxines Alimentaires, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF) |
| المصدر: | Journal of Neurochemistry Journal of Neurochemistry, 2008, 107 (4), pp.952-63. ⟨10.1111/j.1471-4159.2008.05677.x⟩ |
| بيانات النشر: | Wiley, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, MESH: Muscle Cells, Patch-Clamp Techniques, alpha7 Nicotinic Acetylcholine Receptor, MESH: Drug Interactions, MESH: Bivalvia, Gene Expression, Receptors, Nicotinic, Synaptic Transmission, Biochemistry, Membrane Potentials, MESH: Dose-Response Relationship, Drug, Mice, Xenopus laevis, MESH: Behavior, Animal, Myocyte, Drug Interactions, MESH: Animals, Cells, Cultured, Chromatography, High Pressure Liquid, Behavior, Animal, neuromuscular junction, MESH: Electric Stimulation, Nicotinic acetylcholine receptor, Nicotinic agonist, medicine.anatomical_structure, MESH: Receptors, Nicotinic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Imines, medicine.symptom, Heterocyclic Compounds, 3-Ring, Acetylcholine, Protein Binding, MESH: Cells, Cultured, medicine.drug, MESH: Gene Expression, Hydrocarbons, Cyclic, Biology, Neuromuscular junction, marine phycotoxins, MESH: Oocytes, Cellular and Molecular Neuroscience, MESH: Mice, Inbred C57BL, MESH: Xenopus laevis, MESH: Patch-Clamp Techniques, MESH: Bungarotoxins, MESH: Synaptic Transmission, medicine, Animals, Humans, MESH: Membrane Potentials, MESH: Protein Binding, Homomeric, MESH: Chromatography, High Pressure Liquid, MESH: Mice, Acetylcholine receptor, MESH: Heterocyclic Compounds, 3-Ring, Muscle Cells, MESH: Humans, Dose-Response Relationship, Drug, gymnodimine, MESH: Acetylcholine, Bungarotoxins, muscle nicotinic acetylcholine receptor, Electric Stimulation, MESH: Male, Bivalvia, Mice, Inbred C57BL, MESH: Imines, MESH: Hydrocarbons, Cyclic, nervous system, Mechanism of action, Oocytes, Biophysics, MESH: Neuromuscular Junction, neuronal nicotinic receptors, human activities, Neuroscience |
| الوصف: | Gymnodimines (GYMs) are phycotoxins exhibiting unusual structural features including a spirocyclic imine ring system and a trisubstituted tetrahydrofuran embedded within a 16-membered macrocycle. The toxic potential and the mechanism of action of GYM-A, highly purified from contaminated clams, have been assessed. GYM-A in isolated mouse phrenic hemidiaphragm preparations produced a concentration- and time-dependent block of twitch responses evoked by nerve stimulation, without affecting directly elicited muscle twitches, suggesting that it may block the muscle nicotinic acetylcholine (ACh) receptor (nAChR). This was confirmed by the blockade of miniature endplate potentials and the recording of subthreshold endplate potentials in GYM-A paralyzed frog and mouse isolated neuromuscular preparations. Patch-clamp recordings in Xenopus skeletal myocytes revealed that nicotinic currents evoked by constant iontophoretical ACh pulses were blocked by GYM-A in a reversible manner. GYM-A also blocked, in a voltage-independent manner, homomeric human alpha7 nAChR expressed in Xenopus oocytes. Competition-binding assays confirmed that GYM-A is a powerful ligand interacting with muscle-type nAChR, heteropentameric alpha3beta2, alpha4beta2, and chimeric alpha7-5HT(3) neuronal nAChRs. Our data show for the first time that GYM-A broadly targets nAChRs with high affinity explaining the basis of its neurotoxicity, and also pave the way for designing specific tests for accurate GYM-A detection in shellfish samples. |
| تدمد: | 1471-4159 0022-3042 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b2610f753272b6fe9c94785290f40afTest https://doi.org/10.1111/j.1471-4159.2008.05677.xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9b2610f753272b6fe9c94785290f40af |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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