title: Delta-atracotoxins from Australian funnel-web spiders compete with scorpion alpha-toxin binding on both rat brain and insect sodium channels.
abstract: Atracotoxins are novel peptide toxins from the venom of Australian funnel-web spiders that slow sodium current inactivation in a similar manner to scorpion alpha-toxins. To analyse their interaction with known sodium channel neurotoxin receptor sites we determined their effect on scorpion toxin, batrachotoxin and saxitoxin binding. Nanomolar concentrations of delta-atracotoxin-Hv1 and delta-atracotoxin-Ar1 completely inhibited the binding of the scorpion alpha-toxin AaH II to rat brain synaptosomes as well as the binding of LqhalphaIT, a scorpion alpha-toxin highly active on insects, to cockroach neuronal membranes. Moreover, delta-atracotoxin-Hv1 cooperatively enhanced batrachotoxin binding to rat brain synaptosomes in an analogous fashion to scorpion alpha-toxins. Thus the delta-atracotoxins represent a new class of toxins which bind to both mammalian and insect sodium channels at sites similar to, or partially overlapping with, the receptor binding sites of scorpion alpha-toxins.
authors.affiliation: Department of Health Sciences, University of Technology, Broadway, NSW, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Little
authors.forename: H
authors.initials: H
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Zappia
authors.forename: S
authors.initials: S
authors.lastname: Cestèle
authors.forename: M I
authors.initials: MI
authors.lastname: Tyler
authors.forename: M F
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: D
authors.initials: D
authors.lastname: Gordon
authors.forename: G M
authors.initials: GM
authors.lastname: Nicholson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism / Q000633:toxicity; D001667:Binding, Competitive; D001681:Biological Assay; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003058:Cockroaches; D005260:Female; D007313:Insecta; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D030162:Reptilian Proteins; D012530:Saxitoxin / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000378:metabolism* / Q000494:pharmacology; D013112:Spiders; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D001496:Batrachotoxins; D007457:Iodine Radioisotopes; C065190:LqhalphaIT toxin; D009498:Neurotoxins; D030162:Reptilian Proteins; D012604:Scorpion Venoms; D015222:Sodium Channels; D013111:Spider Venoms; D012530:Saxitoxin; C053969:scorpion toxin II, Androctonus; C031775:batrachotoxinin A 20-alpha-benzoate