title: Spiders of medical importance in the Asia-Pacific: atracotoxin, latrotoxin and related spider neurotoxins.
abstract: 1. The spiders of medical importance in the Asia-Pacific region include widow (family Theridiidae) and Australian funnel-web spiders (subfamily Atracinae). In addition, cupboard (family Theridiidae) and Australian mouse spiders (family Actinopodidae) may contain neurotoxins responsible for serious systemic envenomation. Fortunately, there appears to be extensive cross-reactivity of species-specific widow spider antivenom within the family Theridiidae. Moreover, Sydney funnel-web antivenom has been shown to be effective in the treatment of mouse spider envenomation. 2. alpha-Latrotoxin (alpha-LTx) appears to be the main neurotoxin responsible for the envenomation syndrome known as "latrodectism" following bites from widow spiders. This 120 kDa protein binds to distinct receptors (latrophilin 1 and neurexins) to induce neurotransmitter vesicle exocytosis via both Ca2+-dependent and -independent mechanisms, resulting in vesicle depletion. This appears to involve disruption to a process that normally inhibits vesicle fusion in the absence of Ca2+. Precise elucidation of the mechanism of action of alpha-LTx will lead to a major advancement in our understanding of vesicle exocytosis. 3. delta-Atracotoxins (delta-ACTX) are responsible for the primate-specific envenomation syndrome seen following funnel-web spider envenomation. These peptides induce spontaneous repetitive firing and prolongation of action potentials in excitable cells. This results from a hyperpolarizing shift of the voltage-dependence of activation and a slowing of voltage-gated Na+ channel inactivation. This action is due to voltage-dependent binding to neurotoxin receptor site-3 on insect and mammalian voltage-gated Na+ channels in a manner similar, but not identical, to scorpion alpha-toxins and sea anemone toxins. delta-Atracotoxins provide us with highly specific tools to study Na+ channel structure and function 4. omega- and Janus-faced ACTX, from funnel-web spider venom, are novel neurotoxins that show selective toxicity to insects. In particular omega-ACTX define a new insecticide target due to a specific action to block insect voltage-gated Ca2+ channels. Both these ACTX show promise for the development of baculoviral recombinant biopesticides expressing these toxins for the control of insecticide-resistant agricultural pests. In addition, they should provide valuable tools for the pharmacological and structural characterization of insecticide targets.
authors.affiliation: Neurotoxin Research Group, Department of Heath Sciences, University of Technology, PO Box 123, Sydney, Broadway, New South Wales 2007, Australia. Graham.Nicholson@uts.edu.au
authors.forename: Graham M
authors.initials: GM
authors.lastname: Nicholson
authors.forename: Andis
authors.initials: A
authors.lastname: Graudins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000997:Antivenins / Q000627:therapeutic use; D001208:Asia; D001315:Australia; D001740:Black Widow Spider; D006801:Humans; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D010139:Pacific Islands; D017386:Sequence Homology, Amino Acid; D001098:Spider Bites / Q000188:drug therapy / Q000209:etiology*; D013111:Spider Venoms / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D013112:Spiders / Q000235:genetics
chemical_list: D000997:Antivenins; D009498:Neurotoxins; D013111:Spider Venoms