Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells

• Published in: PloS one Vol. 3; no. 10; p. e3448
• Main Authors: Mattei, César, Wen, Peter J, Nguyen-Huu, Truong D, Alvarez, Martha, Benoit, Evelyne, Bourdelais, Andrea J, Lewis, Richard J, Baden, Daniel G, Molgó, Jordi, Meunier, Frédéric A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.10.2008; Public Library of Science (PLoS)
• Subjects: Adrenal glands; Animals; Antidotes; Antidotes - pharmacology; Asthma; Barium; Binding sites; Brevetoxins; Calcium; Calcium - metabolism; Catecholamine; Catecholamines; Catecholamines - secretion; Cattle; Cell Biology/Neuronal Signaling Mechanisms; Channels; Chemical Biology; Chromaffin Cells; Chromaffin Cells - drug effects; Chromaffin Cells - secretion; Ciguatera; Ciguatera Poisoning; Ciguatera Poisoning - drug therapy; Ciguatoxin; Ciguatoxins; Ciguatoxins - pharmacology; Dinoflagellates; Electric potential; Gymnothorax javanicus; Life Sciences; Marine toxins; Microorganisms; Neuroblastoma; Neurological Disorders/Neuropharmacology; Neurons and Cognition; Neurosecretion; Neurosecretion - drug effects; Neurotoxicity; Neurotransmitter release; Nicotine; Rodents; Secretion; Shellfish; SNAP receptors; Sodium; Sodium - metabolism; Sodium Channels; Sodium channels (voltage-gated); Tetanus; Tetrodotoxin; Therapeutic applications; Thiopental; Thiopental - analogs & derivatives; Thiopental - pharmacology; Thiopental - therapeutic use; North Carolina; Queensland Australia; Australia; France; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003448

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 beta-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.