Ciguatoxin extracted from poisonous moray eels Gymnothorax javanicus triggers acetylcholine release from Torpedo cholinergic synaptosomes via reversed Na+ –Ca2+ exchange

Molgó, Jordi; Gaudry-Talarmain, Yvette Morot; Legrand, Anne; Moulian, Nathalie

doi:10.1016/0304-3940(93)9000-4

Cited by 31 publications

(16 citation statements)

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“…Intracellular Na + was monitored in chromaffin cells pre-loaded with the cell-permeant Na + -indicator sodium green. Experiments were performed in a Ca 2+ -free medium containing EGTA (2 mM) to avoid activation of the Na + /Ca 2+ exchanger [13]. Exposure of sodium green loaded chromaffin cells to P-CTX-1B (50 nM) resulted in a slow albeit significant increase in intracellular fluorescence intensity that steadily developed continuously for more than 60 min (Figure 1A, B).…”

Section: Resultsmentioning

confidence: 99%

“…These cyclic polyethers compounds modify Na + current by shifting the voltage-dependency of Na + channel activation towards more negative values, and by partly suppressing their inactivation [8], [24]. There are a variety of functional consequences to promoting such Na + influx in excitable cells: trains of spontaneous action potentials, volume increase of nodal region of frog myelinated nerve fibres [8], [25], [26], enhancement of neurotransmitter release, volume increase of motor nerve terminals at the frog neuromuscular junction [9], [25], spontaneous activity in neuroblastoma cells [23], activation of the Na + /Ca 2+ exchanger in the reversed mode followed by neurotransmitter release from synaptosomes [13], and Ca 2+ mobilisation in neuroblastoma cells [12]. It was therefore important to clarify the effects of such a Na + channel activator on intracellular concentrations of Na + and Ca 2+ and neurotransmitter release.…”

Section: Discussionmentioning

confidence: 99%

“…One of the possible hypotheses is that ciguatoxins promote Ca 2+ entry in nerve terminals, which could in turn stimulate exocytosis. Importantly, the activation of Na + channels by P-CTX-1B has been shown to lead to direct mobilisation of Ca 2+ from internal stores in neuroblastoma cells and rat myotubes [11], [12] and to an indirect activation of the Na + /Ca 2+ exchanger in the reversed mode in cholinergic synaptosomes, allowing Ca 2+ influx against Na + efflux [13].…”

Section: Introductionmentioning

confidence: 99%

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Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

et al. 2008

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Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and β-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

et al. 2008

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“…Overall, inhibition of neuronal potassium channels by ciguatoxins is likely to act in concert with effects on Na v to increase neuronal excitability (Molgo et al 1991(Molgo et al , 1992(Molgo et al , 1993aLewis et al 2000). For example, while intraplantar administration of P-CTX-1 and P-CTX-3 elicits profound cold allodynia, injection of the related site 5 toxin brevetoxin and the sodium channel activator veratridine only elicits spontaneous pain (Zimmermann et al 2013); nodal swelling induced by P-CTX-1B in frog neurons is partially dependent on K + efflux (Mattei et al 2014a), and block of voltage-gated potassium channels by P-CTX-1 contributes to increased neuronal excitability in rat sensory neurons (Birinyi-Strachan et al 2005b).…”

Section: Ciguatoxin Mode Of Actionmentioning

confidence: 98%

Ciguatoxin and Ciguatera

Lewis

Vetter

2016

Marine and Freshwater Toxins

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“…this causes membrane depolarization and functional impairment of excitable cells (Boyarsky and Rayner, 1970;Setliff et al, 1971;Bidard et al, 1984;lombet et al, 1987;Catterall et al, 2007). Secondary responses observed in cells exposed to Ctx-group toxins include Ca 2+ entry into the cell by reverse action of Na + /Ca 2+ exchangers (lewis and endean, 1986;Molgo et al, 1993;terao, 2000), which leads to muscular contraction and neurotransmitter release in a variety of experimental systems (Kakizaki et al, 2006). However, as noted by Dickey and Plakas, not all symptoms observed in exposed humans can be explained by the interaction of Ctx with the NaV, thereby emphasizing that a better understanding of the symptomatology observed in patients and the respective Ctx concentrations to which the patient was exposed is required in order to identify ter methods can also be applied to calcium mediated cell death scenarios, which are relevant to the action of ASP toxins.…”

Section: Ciguatera Fish Poisoning (Cfp)mentioning

confidence: 99%

A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems

Daneshian

2013

ALTEX

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Summary Aquatic food accounts for over 40% of global animal food products, and the potential contamination with toxins of algal origin -marine biotoxins -poses a health threat for consumers. The gold standards to assess toxins in aquatic food have traditionally been in vivo methodssingle marine biotoxins or combinations of marine biotoxins and intoxication symptomatology as well as monitoring the "success" of controls implemented during fishery and aquaculture production, processing, and retailing. For this reason, a workshop was organized in ermatingen, Switzerland by the Center for Alternatives to Animal testing -europe (CAAteurope) within the framework of the transatlantic think tank for toxicology (t 4 ).In contrast to other food products where hygiene and potential contamination with microbes or mold toxins is the prime issue, the emphasis in aquatic products (shellfish and finfish) is, beyond viral and bacterial contaminations, primarily placed on potential contamination with marine biotoxins owing to the numerous and recurring human intoxications.The gold standards to assess toxins in aquatic food have traditionally been in vivo methods, i.e., the mouse and the rat bioassays. Besides the ethical issues of in vivo bioassays there are specific difficulties, e.g., different exposure route (i.p. versus oral), low inter-species comparability, high intra-species variability, and questionable extrapolation of quantitative risk to humans, thus highlighting the need for the development of more reliable detection and quantification methods. Based on this reasoning, the european Food Safety Authority (eFSA) advocates the use of an analytical method, i.e., LC-MS (Liquid Chromatography coupled Mass Spectrometry), as a substitute for in vivo bioassays for almost all classes of marine toxins. However, although lC-MS is a very sensitive method that has the advantages of being able to detect multiple toxins in a single analysis and being good for confirming the identity of toxins, the quality of quantitative analysis is dependent on the availability of calibration standards. While many new toxin structural analogues have been detected and identified using LC-MS, this technique -as with most other methods -is not good at detecting new toxin types. When new toxin analogues are detected but accurate standards are not yet available, only an approximate quantitation is possible using estimated response factors.For the purpose of risk assessment of food, however, it is imperative to focus on the possible adverse effects, independent of whether they stem from one toxin or a combination of toxins. As toxicity is defined by functional and structural changes of biological systems, the development of a human-relevant in vitro system for appropriate risk assessment of marine biotoxins in seafood stands to reason. Moreover, poor correlation of human intoxications, of acute symptomatology and long-term adverse effects, and of predictive in vitro, in vivo, and analytical detection methodologies of marine biotoxins stems not least from a...

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Ciguatoxin extracted from poisonous moray eels Gymnothorax javanicus triggers acetylcholine release from Torpedo cholinergic synaptosomes via reversed Na+ –Ca2+ exchange

Cited by 31 publications

References 0 publications

Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

Ciguatoxin and Ciguatera

A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems

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