Description
Brevetoxinsarelipid-solublepolyetherneurotoxinsinitiallyproducedbythedinoflagellateKareniabrevis.BrevetoxinsactasagoNISTs,bindingtheneurotoxinsite5onSCN4A/Nav1.4andSCN5A/Nav1.5voltage-gatedNa+channelsinskeletalmuscleandcardiactissue,producingachannelopeningeffect;thisactivityresultsinbronchoconstrictionandairwayinflammationinvivo.Stimulationofthevoltage-gatedNa+channelsalsoinducesNMDAreceptor-mediatedreleaseofL-glutamateandL-aspartateinneurons.ActivityatthesechannelsalsoactivatesPyk2andSrc,inducingdownstreamsignalingcascades.Brevetoxin2formsDNAadductswithcytidineinisolatedlungcellsandwithadenosineandguanosineinvivo,indicatingcarcinogenicactivity.
References
ZaiasJ,FlemingLE,BadenDG,etal.Repeatedexposuretoaerosolizedbrevetoxin-3inducesprolongedairwayhyperresponsivenessandlunginflammationinsheep.InhalToxicol.2011Mar;23(4):205-11.PMID:21456953.
LiberonaJL,CárdenasJC,ReyesR,etal.Sodium-dependentactionpotentialsinducedbybrevetoxin-3triggerbothIP3increaseandintracellularCa2+releaseinratskeletalmyotubes.CellCalcium.2008Sep;44(3):289-97.PMID:18276006.
RadwanFF,RamsdellJS.BrevetoxinformscovalentDNAadductsinratlungfollowingintratrachealexposure.EnvironHealthPerspect.2008Jul;116(7):930-6.PMID:18629316.
CaoZ,GeorgeJ,BadenDG,etal.Brevetoxin-inducedphosphorylationofPyk2andSrcinmurineneocorticalneuronsinvolvesdistinctsignalingpathways.BrainRes.2007Dec12;1184:17-27.PMID:17963734.
BotteinDechraouiMY,RamsdellJS.TypeBbrevetoxinsshowtissueselectivityforvoltage-gatedsodiumchannels:comparisonofbrain,skeletalmuscleandcardiacsodiumchannels.Toxicon.2003Jun;41(7):919-27.PMID:12782093.
BermanFW,MurrayTF.Brevetoxinscauseacuteexcitotoxicityinprimaryculturesofratcerebellargranuleneurons.JPharmacolExpTher.1999Jul;290(1):439-44.PMID:10381810.
