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Article

Prorocentrolide-A from Cultured Prorocentrum lima Dinoflagellates Collected in Japan Blocks Sub-Types of Nicotinic Acetylcholine Receptors

1
Commissariat à l’énergie Atomique et aux énergies Alternatives (CEA), Institut des Sciences du Vivant Frédéric Joliot, Service d’Ingénierie Moléculaire des Protéines, Université Paris-Saclay, Bâtiment 152, 91191 Gif-sur-Yvette, France
2
Institut des Neurosciences Paris-Saclay, UMR 9197 CNRS-Université Paris-Sud, 91198 Gif-sur-Yvette, France
3
CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, Labex LERMIT, 91198 Gif-sur-Yvette, France
4
Japan Food Research Laboratories, 6-11-10 Nagayama, Tama, Tokyo 206-0025, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxins 2018, 10(3), 97; https://doi.org/10.3390/toxins10030097
Received: 29 January 2018 / Revised: 19 February 2018 / Accepted: 23 February 2018 / Published: 28 February 2018
(This article belongs to the Special Issue Public Health Outreach to Prevention of Aquatic Toxin Exposure)
Prorocentrolides are members of the cyclic imine phycotoxins family. Their chemical structure includes a 26-membered carbo-macrocycle and a 28-membered macrocyclic lactone arranged around a hexahydroisoquinoline that incorporates the characteristic cyclic imine group. Six prorocentrolides are already known. However, their mode of action remains undetermined. The aim of the present work was to explore whether prorocentrolide-A acts on nicotinic acetylcholine receptors (nAChRs), using competition-binding assays and electrophysiological techniques. Prorocentrolide-A displaced [125I]α-bungarotoxin binding to Torpedo membranes, expressing the muscle-type (α12β1γδ) nAChR, and in HEK-293 cells, expressing the chimeric chick neuronal α7-5HT3 nAChR. Functional studies revealed that prorocentrolide-A had no agonist action on nAChRs, but inhibited ACh-induced currents in Xenopus oocytes that had incorporated the muscle-type α12β1γδ nAChR to their membranes, or that expressed the human α7 nAChR, as revealed by voltage-clamp recordings. Molecular docking calculations showed the absence of the characteristic hydrogen bond between the iminium group of prorocentrolide-A and the backbone carbonyl group of Trp147 in the receptor, explaining its weaker affinity as compared to all other cyclic imine toxins. In conclusion, this is the first study to show that prorocentrolide-A acts on both muscle and neuronal nAChRs, but with higher affinity on the muscle-type nAChR. View Full-Text
Keywords: prorocentrolides; dinoflagellate toxin; cyclic imine toxins; nicotinic acetylcholine receptors; Xenopus oocytes; nicotinic currents; binding assays; molecular docking prorocentrolides; dinoflagellate toxin; cyclic imine toxins; nicotinic acetylcholine receptors; Xenopus oocytes; nicotinic currents; binding assays; molecular docking
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MDPI and ACS Style

Amar, M.; Aráoz, R.; Iorga, B.I.; Yasumoto, T.; Servent, D.; Molgó, J. Prorocentrolide-A from Cultured Prorocentrum lima Dinoflagellates Collected in Japan Blocks Sub-Types of Nicotinic Acetylcholine Receptors. Toxins 2018, 10, 97. https://doi.org/10.3390/toxins10030097

AMA Style

Amar M, Aráoz R, Iorga BI, Yasumoto T, Servent D, Molgó J. Prorocentrolide-A from Cultured Prorocentrum lima Dinoflagellates Collected in Japan Blocks Sub-Types of Nicotinic Acetylcholine Receptors. Toxins. 2018; 10(3):97. https://doi.org/10.3390/toxins10030097

Chicago/Turabian Style

Amar, Muriel, Rómulo Aráoz, Bogdan I. Iorga, Takeshi Yasumoto, Denis Servent, and Jordi Molgó. 2018. "Prorocentrolide-A from Cultured Prorocentrum lima Dinoflagellates Collected in Japan Blocks Sub-Types of Nicotinic Acetylcholine Receptors" Toxins 10, no. 3: 97. https://doi.org/10.3390/toxins10030097

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