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

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Daniel G Baden, Director (Creator)
Andrea J. Bourdelais, Research Associate Professor (Creator)
Institution
The University of North Carolina Wilmington (UNCW )
Web Site: http://library.uncw.edu/

Abstract: 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 ß-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.

Additional Information

Publication
Mattei C, Wen PJ, Nguyen-Huu TD, Alvarez M, Benoit E, et al. (2008). Brevenal inhibits Pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells. PLoS ONE 3(10): e3448. doi:10.1371/journal.pone.0003448. © 2008 Mattei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Language: English
Date: 2009
Keywords
Neurosecretion, Neurotransmitters, Poisonous fishes--Toxicology
Subjects
Poisonous fishes--Toxicology
Neurosecretion
Neurotransmitters