Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.6
4.9
Journals
Marine Drugs
Special Issues
Marine Toxins Affecting Cholinergic System
share announcement

Marine Toxins Affecting Cholinergic System

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (27 September 2019) | Viewed by 27930

Special Issue Editors

Prof. Dr. Tom Turk

E-Mail Website
Guest Editor
Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
Interests: marine natural compounds; antifouling; toxicity; coatings; environment
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. William R. Kem

E-Mail Website
Guest Editor
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, FL, USA
Interests: marine toxins; including nemertine toxins acting on cholinergic system; cognition; treatment of Alzheimer disease; addictive behavior; schizophrenia

Special Issue Information

Dear Colleagues,

This Special Issue on “Marine Toxins Affecting Cholinergic Systems” will focus on marine toxins and other marine natural compounds which interfere with cholinergic systems. Among possible sources of such compounds, which have been already identified as producers, are dinoflagellate toxins, marine sponges, nemerteans, bryozoans, soft corals, and peptides from cone snails. Papers using marine compounds that act as agonists/antagonists/inhibitors/modulators on peripheral cholinergic systems, as well as those affecting various nicotinic acetylcholine receptors in the central nervous system or in cancer cells are welcome. We are especially interested in studies that report on the involvement of cholinergic system and interfering compounds with cell signalling. Papers that describe the possible therapeutic uses of such compounds are also welcome.

As Guest Editors of this Special Issue of Marine Drugs, we invite you to provide your valuable contributions to this Special Issue on “Marine Toxins Affecting Cholinergic Systems”.

Sincerely yours,

Prof. Tom Turk
Prof. William R. Kem
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • toxins
  • marine natural compounds
  • nAChR
  • cholinergic system
  • cancer
  • cognition
  • cell signaling
  • inflammation
  • pain

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

12 pages, 2359 KiB  
Article
A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine
by Hong Xing, Sunil Keshwah, Anne Rouchaud and William R. Kem
Mar. Drugs 2020, 18(2), 106; https://doi.org/10.3390/md18020106 - 11 Feb 2020
Cited by 15 | Viewed by 3554
Abstract
Many organisms possess “secondary” compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other “minor” compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we [...] Read more.
Many organisms possess “secondary” compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other “minor” compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we present an initial in vitro investigation of the actions of two isomeric tetrahydropyridyl ring-containing anabasine analogs: isoanatabine, an alkaloid isolated from a marine worm, and anatabine, a relatively abundant minor alkaloid in commercial tobacco plants. Both compounds have a double bond that is distal to the piperidine ring nitrogen of anabasine. Racemic isoanatabine and anatabine were synthesized and their S- and R-enantiomers were isolated by chiral high pressure liquid chromatography (HPLC). Both isoanatabines displayed higher efficacies at α4β2 nicotinic acetylcholine receptors (nAChRs) relative to the anatabines; R-isoanatabine was most potent. Radioligand binding experiments revealed similar α4β2 nAChR binding affinities for the isoanatabines, but R-anatabine affinity was twice that of S-anatabine. While the two anatabines and S-isoanatabine were highly efficacious agonists at α7 nAChRs, R-isoanatabine was only a weak partial agonist. The four compounds share an ability to stimulate both α4β2 and α7 nAChRs, a property that may be useful in developing more efficacious drugs to treat neurodegenerative and other medical disorders. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

12 pages, 1253 KiB  
Article
Investigation of the Possible Pharmacologically Active Forms of the Nicotinic Acetylcholine Receptor Agonist Anabaseine
by Kristin Andrud, Hong Xing, Bjarne Gabrielsen, Linda Bloom, Vladimir Mahnir, Stephen Lee, Benedict T. Green, Jon Lindstrom and William Kem
Mar. Drugs 2019, 17(11), 614; https://doi.org/10.3390/md17110614 - 29 Oct 2019
Cited by 8 | Viewed by 2993
Abstract
Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence [...] Read more.
Three major forms of the nicotinic agonist toxin anabaseine (cyclic iminium, cyclic imine and the monocationic open-chain ammonium-ketone) co-exist in almost equal concentrations at physiological pH. We asked the question: Which of these forms is pharmacologically active? First, we investigated the pH dependence of anabaseine inhibition of [3H]-methylcarbamylcholine binding at rat brain α4β2 nicotinic acetylcholine receptors (nAChRs). These experiments indicated that one or both monocationic forms interact with the orthosteric binding site for ACh. However, since they occur at equal concentrations near physiological pH, we employed another approach, preparing a stable analog of each form and examining its agonist activities and binding affinities at several vertebrate brain and neuromuscular nAChRs. Only 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine monohydrogen chloride (PTHP), the cyclic iminium analog, displayed nAChR potencies and binding affinities similar to anabaseine. The cyclic imine analog 2,3′-bipyridyl and the open-chain ammonium-ketone analog 5-methylamino-1-(3-pyridyl)-1-pentanone (MAPP), displayed ≤1% of the activity predicted if the one form was solely active. The lower potency of weakly basic 2,3′-bipyridyl can be explained by the presence of a small concentration of its monocationic form. Since the open chain ammonium-ketone monocationic form of anabaseine has some structural similarity to the neurotransmitter GABA, we also tested the ability of anabaseine and its 1,2-dehydropyrrolidinyl analog myosmine to activate a mammalian GABAA receptor, but no activity was detected. We conclude that the monocationic cyclic iminium is the form which avidly binds and activates vertebrate nAChRs. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

17 pages, 3245 KiB  
Article
Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro
by Evelyne Benoit, Aurélie Couesnon, Jiri Lindovsky, Bogdan I. Iorga, Rómulo Aráoz, Denis Servent, Armen Zakarian and Jordi Molgó
Mar. Drugs 2019, 17(5), 306; https://doi.org/10.3390/md17050306 - 24 May 2019
Cited by 12 | Viewed by 3569
Abstract
Pinnatoxins (PnTXs) A-H constitute an emerging family belonging to the cyclic imine group of phycotoxins. Interest has been focused on these fast-acting and highly-potent toxins because they are widely found in contaminated shellfish. Despite their highly complex molecular structure, PnTXs have been chemically [...] Read more.
Pinnatoxins (PnTXs) A-H constitute an emerging family belonging to the cyclic imine group of phycotoxins. Interest has been focused on these fast-acting and highly-potent toxins because they are widely found in contaminated shellfish. Despite their highly complex molecular structure, PnTXs have been chemically synthetized and demonstrated to act on various nicotinic acetylcholine receptor (nAChR) subtypes. In the present work, PnTX-A, PnTX-G and analogue, obtained by chemical synthesis with a high degree of purity (>98%), have been studied in vivo and in vitro on adult mouse and isolated nerve-muscle preparations expressing the mature muscle-type (α1)2β1δε nAChR. The results show that PnTX-A and G acted on the neuromuscular system of anesthetized mice and blocked the compound muscle action potential (CMAP) in a dose- and time-dependent manner, using a minimally invasive electrophysiological method. The CMAP block produced by both toxins in vivo was reversible within 6–8 h. PnTX-A and G, applied to isolated extensor digitorum longus nerve-muscle preparations, blocked reversibly isometric twitches evoked by nerve stimulation. The action of PnTX-A was reversed by 3,4-diaminopyridine. Both toxins exerted no direct action on muscle fibers, as revealed by direct muscle stimulation. PnTX-A and G blocked synaptic transmission at mouse neuromuscular junctions and PnTX-A amino ketone analogue (containing an open form of the imine ring) had no effect on neuromuscular transmission. These results indicate the importance of the cyclic imine for interacting with the adult mammalian muscle-type nAChR. Modeling and docking studies revealed molecular determinants responsible for the interaction of PnTXs with the muscle-type nAChR. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

14 pages, 1914 KiB  
Article
Cervical Cancer Correlates with the Differential Expression of Nicotinic Acetylcholine Receptors and Reveals Therapeutic Targets
by Yiqiao Liu, Jiang Qian, Zhihua Sun, Dongting Zhangsun and Sulan Luo
Mar. Drugs 2019, 17(5), 256; https://doi.org/10.3390/md17050256 - 28 Apr 2019
Cited by 21 | Viewed by 3917
Abstract
Nicotinic acetylcholine receptors (nAChRs) are associated with various cancers, but the relation between nAChRs and cervical cancer remains unclear. Therefore, this study investigated the differential expression of nAChR subunits in human cervical cancer cell lines (SiHa, HeLa, and CaSki) and in normal ectocervical [...] Read more.
Nicotinic acetylcholine receptors (nAChRs) are associated with various cancers, but the relation between nAChRs and cervical cancer remains unclear. Therefore, this study investigated the differential expression of nAChR subunits in human cervical cancer cell lines (SiHa, HeLa, and CaSki) and in normal ectocervical cell lines (Ect1/E6E7) at mRNA and protein levels. Two specific nAChR subtype blockers, αO-conotoxin GeXIVA and α-conotoxin TxID, were then selected to treat different human cervical cancer cell lines with specific nAChR subtype overexpression. The results showed that α3, α9, α10, and β4 nAChR subunits were overexpressed in SiHa cells compared with that in normal cells. α9 and α10 nAChR subunits were overexpressed in CaSki cells. α*-conotoxins that targeted either α9α10 or α3β4 nAChR were able to significantly inhibit cervical cancer cell proliferation. These findings may provide a basis for new targets for cervical cancer targeted therapy. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

15 pages, 3942 KiB  
Article
Identification of Novel Gymnodimines and Spirolides from the Marine Dinoflagellate Alexandrium ostenfeldii
by Christian Zurhelle, Joyce Nieva, Urban Tillmann, Tilmann Harder, Bernd Krock and Jan Tebben
Mar. Drugs 2018, 16(11), 446; https://doi.org/10.3390/md16110446 - 14 Nov 2018
Cited by 43 | Viewed by 5422
Abstract
Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of [...] Read more.
Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of four novel cyclic-imine toxins (two gymnodimines (GYMs) and two spirolides (SPXs)) from cultures of Alexandrium ostenfeldii. A GYM with m/z 510 (1) was identified as 16-desmethylGYM D. A GYM with m/z 526 was identified as the hydroxylated degradation product of (1) with an exocyclic methylene at C-17 and an allylic hydroxyl group at C-18. This compound was named GYM E (2). We further identified a SPX with m/z 694 as 20-hydroxy-13,19-didesmethylSPX C (10) and a SPX with m/z 696 as 20-hydroxy-13,19-didesmethylSPX D (11). This is the first report of GYMs without a methyl group at ring D and SPXs with hydroxyl groups at position C-20. These compounds can be conceived as derivatives of the same nascent polyketide chain, supporting the hypothesis that GYMs and SPXs are produced through common biosynthetic genes. Both novel GYMs 1 and 2 were detected in significant amounts in extracts from natural plankton assemblages (1: 447 pg; 2: 1250 pg; 11: 40 pg per mL filtered seawater respectively). Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

17 pages, 4467 KiB  
Article
APS8 Delays Tumor Growth in Mice by Inducing Apoptosis of Lung Adenocarcinoma Cells Expressing High Number of α7 Nicotinic Receptors
by Sabina Berne, Maja Čemažar, Robert Frangež, Polona Juntes, Simona Kranjc, Marjana Grandič, Monika Savarin and Tom Turk
Mar. Drugs 2018, 16(10), 367; https://doi.org/10.3390/md16100367 - 3 Oct 2018
Cited by 9 | Viewed by 3313
Abstract
The alkylpyridinium polymer APS8, a potent antagonist of α7 nicotinic acetylcholine receptors (nAChRs), selectively induces apoptosis in non-small cell lung cancer cells but not in normal lung fibroblasts. To explore the potential therapeutic value of APS8 for at least certain types of lung [...] Read more.
The alkylpyridinium polymer APS8, a potent antagonist of α7 nicotinic acetylcholine receptors (nAChRs), selectively induces apoptosis in non-small cell lung cancer cells but not in normal lung fibroblasts. To explore the potential therapeutic value of APS8 for at least certain types of lung cancer, we determined its systemic and organ-specific toxicity in mice, evaluated its antitumor activity against adenocarcinoma xenograft models, and examined the in-vitro mechanisms of APS8 in terms of apoptosis, cytotoxicity, and viability. We also measured Ca2+ influx into cells, and evaluated the effects of APS8 on Ca2+ uptake while siRNA silencing of the gene for α7 nAChRs, CHRNA7. APS8 was not toxic to mice up to 5 mg/kg i.v., and no significant histological changes were observed in mice that survived APS8 treatment. Repetitive intratumoral injections of APS8 (4 mg/kg) significantly delayed growth of A549 cell tumors, and generally prevented regrowth of tumors, but were less effective in reducing growth of HT29 cell tumors. APS8 impaired the viability of A549 cells in a dose-dependent manner and induced apoptosis at micro molar concentrations. Nano molar APS8 caused minor cytotoxic effects, while cell lysis occurred at APS8 >3 µM. Furthermore, Ca2+ uptake was significantly reduced in APS8-treated A549 cells. Observed differences in response to APS8 can be attributed to the number of α7 nAChRs expressed in these cells, with those with more AChRs (i.e., A549 cells) being more sensitive to nAChR antagonists like APS8. We conclude that α7 nAChR antagonists like APS8 have potential to be used as therapeutics for tumors expressing large numbers of α7 nAChRs. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Figure 1

Review

Jump to: Research

13 pages, 1156 KiB  
Review
Pinnatoxins’ Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health
by Nicolas Delcourt, Emmeline Lagrange, Eric Abadie, Valérie Fessard, Jean-Marc Frémy, Jean-Paul Vernoux, Marie-Bénédicte Peyrat, Thomas Maignien, Nathalie Arnich, Jordi Molgó and César Mattei
Mar. Drugs 2019, 17(7), 425; https://doi.org/10.3390/md17070425 - 20 Jul 2019
Cited by 13 | Viewed by 4445
Abstract
Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No [...] Read more.
Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No human intoxication has been reported to date although acute toxicity was induced by PnTxs in rodents. LD50 values have been estimated for the different PnTXs through the oral route. At sublethal doses, all symptoms are reversible, and no neurological sequelae are visible. These symptoms are consistent with impairment of central and peripheral cholinergic network functions. In fact, PnTXs are high-affinity competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Moreover, their lethal effects are consistent with the inhibition of muscle nAChRs, inducing respiratory distress and paralysis. Human intoxication by ingestion of PnTXs could result in various symptoms observed in episodes of poisoning with natural nAChR antagonists. This review updates the available data on PnTX toxicity with a focus on their mode of action on cholinergic networks and suggests the effects that could be extrapolated on human physiology. Full article
(This article belongs to the Special Issue Marine Toxins Affecting Cholinergic System)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop