2013
DOI: 10.1016/j.hal.2013.03.001
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Brevenal, a brevetoxin antagonist from Karenia brevis, binds to a previously unreported site on mammalian sodium channels

Abstract: Brevetoxins are a family of ladder-frame polyether toxins produced by the marine dinoflagellate Karenia brevis. During blooms of K. brevis, 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 K. brevis 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-sens… Show more

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Cited by 23 publications
(30 citation statements)
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“…A further possible explanation for the differences noted between CBA-N2a and LC-MS/MS data may be that neuro-2a cytotoxicity will actually reflect the complex interactions on voltage-gated sodium channels (VGSCs) exerted by the combination of bioactive compounds present in G. polynesiensis culture extracts. In some instances, this may result in structural or chemical competition, as had been demonstrated for brevenal and brevetoxin in K. brevis [74].…”
Section: Discussionmentioning
confidence: 92%
“…A further possible explanation for the differences noted between CBA-N2a and LC-MS/MS data may be that neuro-2a cytotoxicity will actually reflect the complex interactions on voltage-gated sodium channels (VGSCs) exerted by the combination of bioactive compounds present in G. polynesiensis culture extracts. In some instances, this may result in structural or chemical competition, as had been demonstrated for brevenal and brevetoxin in K. brevis [74].…”
Section: Discussionmentioning
confidence: 92%
“…Gambierol and gambieric acid A inhibit binding of the brevetoxins to the VGSC 23. Brevenal, a non‐toxic molecule containing only five polyether rings binds to the VGSC at a site that is distinct from the brevetoxin site 24. Gambierol is also a potent potassium channel blocker,25 and maitotoxin is a calcium channel activator 26.…”
Section: Discussionmentioning
confidence: 99%
“…This toxin can inhibit respiratory and myocardial function, resulting in spontaneous and repeated dose-dependent muscle contraction, leading to beam tremor, convulsion or jump, dose-related decrease in respiratory rate and bronchoconstriction of central and peripheral nerves. The LD 50 of BTX-2 towards mice is 55.36 mg/kg [55], the toxicity of which is much weaker than that of shellfish-accumulated marine toxins including STX, PTX, TTX. BTX combines with the target site of sodium channel receptor and opening the sodium channel on the excited membrane, the permeability of cell membranes to sodium ion can be enhanced and the voltage-gated sodium channel can be activated.…”
Section: Introductionmentioning
confidence: 96%