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Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean

Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators. Hoplonemerteans have a proboscis armed with one or more stylets used in prey capture and are taxonomically divided into Order Monostilifera, whos...

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Autores principales: Kem, William R., Rocca, James R., Johnson, Jodie V., Junoy, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867080/
https://www.ncbi.nlm.nih.gov/pubmed/36668866
http://dx.doi.org/10.3390/toxins15010046
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author Kem, William R.
Rocca, James R.
Johnson, Jodie V.
Junoy, Juan
author_facet Kem, William R.
Rocca, James R.
Johnson, Jodie V.
Junoy, Juan
author_sort Kem, William R.
collection PubMed
description Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators. Hoplonemerteans have a proboscis armed with one or more stylets used in prey capture and are taxonomically divided into Order Monostilifera, whose members possess a single large proboscis stylet, and Order Polystilifera, whose members have multiple small stylets. Many monostiliferans contain alkaloidal toxins, including anabaseine, that stimulate and then desensitize nicotinic acetylcholine receptors that are present in all animals. These compounds also interact with pyridyl chemoreceptors in crustaceans, reducing predation and larval settlement. Anabaseine has been a lead compound in the design of alpha7 nicotinic acetylcholine receptor agonists like GTS-21 (also called DMXBA) to treat disorders of cognition such as Alzheimer’s disease and schizophrenia. These drug candidates also display anti-inflammatory activities of potential medical importance. Most polystiliferans live deep in open oceans and are relatively inaccessible. We fortunately obtained two live specimens of a large benthic polystiliferan, Paradrepanophorus crassus (Pc), from the coast of Spain. MS and NMR analyses of the Ehrlich’s reagent derivative allowed identification of anabaseine. A spectrophotometric assay for anabaseine, also based on its reaction with Ehrlich’s reagent, revealed high concentrations of anabaseine in the body and proboscis. Apparently, the biosynthetic mechanism for producing anabaseine was acquired early in the evolution of the Hoplonemertea, before the monostiliferan-polystiliferan divergence.
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spelling pubmed-98670802023-01-22 Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean Kem, William R. Rocca, James R. Johnson, Jodie V. Junoy, Juan Toxins (Basel) Article Nemerteans (also called Nemertines) are a phylum of predominantly marine worms that use toxins to capture prey and to defend themselves against predators. Hoplonemerteans have a proboscis armed with one or more stylets used in prey capture and are taxonomically divided into Order Monostilifera, whose members possess a single large proboscis stylet, and Order Polystilifera, whose members have multiple small stylets. Many monostiliferans contain alkaloidal toxins, including anabaseine, that stimulate and then desensitize nicotinic acetylcholine receptors that are present in all animals. These compounds also interact with pyridyl chemoreceptors in crustaceans, reducing predation and larval settlement. Anabaseine has been a lead compound in the design of alpha7 nicotinic acetylcholine receptor agonists like GTS-21 (also called DMXBA) to treat disorders of cognition such as Alzheimer’s disease and schizophrenia. These drug candidates also display anti-inflammatory activities of potential medical importance. Most polystiliferans live deep in open oceans and are relatively inaccessible. We fortunately obtained two live specimens of a large benthic polystiliferan, Paradrepanophorus crassus (Pc), from the coast of Spain. MS and NMR analyses of the Ehrlich’s reagent derivative allowed identification of anabaseine. A spectrophotometric assay for anabaseine, also based on its reaction with Ehrlich’s reagent, revealed high concentrations of anabaseine in the body and proboscis. Apparently, the biosynthetic mechanism for producing anabaseine was acquired early in the evolution of the Hoplonemertea, before the monostiliferan-polystiliferan divergence. MDPI 2023-01-05 /pmc/articles/PMC9867080/ /pubmed/36668866 http://dx.doi.org/10.3390/toxins15010046 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kem, William R.
Rocca, James R.
Johnson, Jodie V.
Junoy, Juan
Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title_full Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title_fullStr Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title_full_unstemmed Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title_short Discovery of the Nicotinic Receptor Toxin Anabaseine in a Polystiliferan Nemertean
title_sort discovery of the nicotinic receptor toxin anabaseine in a polystiliferan nemertean
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867080/
https://www.ncbi.nlm.nih.gov/pubmed/36668866
http://dx.doi.org/10.3390/toxins15010046
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