Brevenal, a Brevetoxin Antagonist from Karenia Brevis, Binds to a Previously Unreported Site on Mammalian Sodium Channels

Overview

Journal Harmful Algae

Publisher Elsevier

Specialties Biology
Environmental Health
Microbiology
Toxicology

Date 2013 Jun 22

PMID 23789024

Citations 9

Authors

Elena P Gold

Henry M Jacocks

Andrea J Bourdelais

Daniel G Baden

Affiliations

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Abstract

Brevetoxins are a family of ladder-frame polyether toxins produced by the marine dinoflagellate . During blooms of , inhalation of brevetoxins aerosolized by wind and wave action can lead to asthma-like symptoms in persons at the beach. Consumption of either shellfish or finfish contaminated by blooms can lead to the development of neurotoxic shellfish poisoning. The toxic effects of brevetoxins are due to binding at a defined site on, and subsequent activation of, voltage-sensitive sodium channels (VSSCs) in cell membranes (site 5). In addition to brevetoxins, produces several other ladder-frame compounds. One of these compounds, brevenal, has been shown to antagonize the effects of brevetoxin. In an effort to further characterize to effects of brevenal, a radioactive analog ([H]-brevenol) was produced by reducing the side-chain terminal aldehyde moiety of brevenal to an alcohol using tritiated sodium borohydride. A K of 67 nM and B of 7.1 pmol/mg protein were obtained for [H]-brevenol in rat brain synaptosomes, suggesting a 1:1 matching with VSSCs. Brevenal and brevenol competed for [H]-brevenol binding with K values of 75 nM and 56 nM, respectively. However, although both brevenal and brevenol can inhibit brevetoxin binding, brevetoxin was completely ineffective at competition for [H]-brevenol binding. After examining other site-specific compounds, it was determined that [H]-brevenol binds to a site that is distinct from the other known sites including the brevetoxin site (site 5) although some interaction with site 5 is apparent.

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