Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes.
The polyether lipid-soluble toxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique site associated with rat brain synaptosomes. Using [3H]brevetoxin PbTx-3 as a specific probe, binding was determined at 4 degrees in rat brain synaptosomes using a rapid centrifugation technique. Rosenthal analysis yields a KD of 2.9 nM and a Bmax of 6.8 pmol of toxin/mg of protein. Labeled probe can be displaced by unlabeled PbTx-3, PbTx-2, or synthetic PbTx-3 (reduced PbTx-2) but not by a nontoxic, synthetic oxidized derivative of PbTx-2. Competition experiments using natural toxin probes specific for sites 1-4 of the voltage-dependent sodium channel have illustrated that PbTx-3 does not bind to any of the previously described sites associated with the channel. A fifth site is proposed. In addition, because of the varied nomenclature associated with the brevetoxins, a new classification system is proposed.
D000157:Aconitine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004141:Dinoflagellida; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008387:Marine Toxins / Q000378:metabolism* / Q000494:pharmacology; D035964:Oxocins; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D014316:Tritium; D000095702:Polyether Toxins
D000157:Aconitine; D007473:Ion Channels; D008387:Marine Toxins; D035964:Oxocins; D012964:Sodium; D014316:Tritium; C041017:brevetoxin T17; D000095702:Polyether Toxins