title: Brevenal is a natural inhibitor of brevetoxin action in sodium channel receptor binding assays.
abstract: 1. Florida red tides produce profound neurotoxicity that is evidenced by massive fish kills, neurotoxic shellfish poisoning, and respiratory distress. Red tides vary in potency, potency that is not totally governed by toxin concentration. The purpose of the study was to understand the variable potency of red tides by evaluating the potential for other natural pharmacological agents which could modulate or otherwise reduce the potency of these lethal environmental events. 2. A synaptosome binding preparation with 3-fold higher specific brevetoxin binding was developed to detect small changes in toxin binding in the presence of potential antagonists. Rodent brain labeled in vitro with tritiated brevetoxin shows high specific binding in the cerebellum as evidenced by autoradiography. Synaptosome binding assays employing cerebellum-derived synaptosomes illustrate 3-fold increased specific binding. 3. A new polyether natural product from Florida's red tide dinoflagellate Karenia brevis, has been isolated and characterized. Brevenal, as the nontoxic natural product is known, competes with tritiated brevetoxin for site 5 associated with the voltage-sensitive sodium channel (VSSC). Brevenal displacement of specific brevetoxin binding is purely competitive in nature. 4. Brevenal, obtained from either laboratory cultures or field collections during a red tide, protects fish from the neurotoxic effects of brevetoxin exposure. 5. Brevenal may serve as a model compound for the development of therapeutics to prevent or reverse intoxication in red tide exposures.
authors.affiliation: Center for Marine Science, University of North Carolina at Wilmington, Wilmington, North Carolina 28409, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Bourdelais
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Henry
authors.initials: H
authors.lastname: Jacocks
authors.forename: Jerome
authors.initials: J
authors.lastname: Naar
authors.forename: Jeffery L C
authors.initials: JL
authors.lastname: Wright
authors.forename: Jigani
authors.initials: J
authors.lastname: Carsi
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Baden
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects* / Q000502:physiology; D001681:Biological Assay; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003532:Cyprinodontiformes; D004141:Dinoflagellida / Q000737:chemistry / Q000378:metabolism*; D004987:Ethers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008387:Marine Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D035964:Oxocins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D026941:Sodium Channel Blockers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects; D013874:Thiopental / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000095702:Polyether Toxins
chemical_list: D004987:Ethers; D008387:Marine Toxins; D035964:Oxocins; D011108:Polymers; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013874:Thiopental; C489035:brevenal (polyether); C004316:thiobutabarbital; C053342:brevetoxin; D000095702:Polyether Toxins