Delta-atracotoxins From Australian Funnel-Web Spiders Compete With Scorpion Alpha-Toxin Binding on Both Rat Brain and Insect Sodium Channels

FEBS Lett. 1998 Nov 20;439(3):246-52. doi: 10.1016/s0014-5793(98)01378-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Batrachotoxins / metabolism
  • Batrachotoxins / toxicity
  • Binding, Competitive
  • Biological Assay
  • Brain / drug effects
  • Brain / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chromatography, High Pressure Liquid
  • Cockroaches
  • Female
  • Insecta
  • Iodine Radioisotopes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity
  • Rats
  • Rats, Wistar
  • Reptilian Proteins
  • Saxitoxin / metabolism
  • Scorpion Venoms / metabolism*
  • Scorpion Venoms / pharmacology
  • Scorpion Venoms / toxicity
  • Scorpions
  • Sequence Homology, Amino Acid
  • Sodium Channels / metabolism*
  • Spider Venoms / metabolism*
  • Spider Venoms / pharmacology
  • Spiders
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Batrachotoxins
  • Iodine Radioisotopes
  • LqhalphaIT toxin
  • Neurotoxins
  • Reptilian Proteins
  • Scorpion Venoms
  • Sodium Channels
  • Spider Venoms
  • Saxitoxin
  • scorpion toxin II, Androctonus
  • batrachotoxinin A 20-alpha-benzoate