Spider toxins as tools for dissecting elements of excitatory amino acid transmission

Abstract

During millions of years of evolution spiders have refined toxins which either paralyse or kill their prey, but it is becoming increasingly clear that many of these chemicals are neurotoxins which affect prey and non-prey alike. Their widespread action throughout the animal kingdom is hardly surprising given the common properties that characterize the excitable systems of most animals, and because of this neuroscientists have been alerted to the potential of these compounds as probes of central and peripheral nervous function. The vast majority of spider species belong to the Suborder Labidognatha which contains the aerial web-weaving spiders. The black widow and red-back spiders ( Latrodectus spp., Family Theridiidae), which are members of this Suborder, are familiar to most neuroscientists by virtue of the powerful proteinaceous, presynaptic toxins that they manufacture, but these are complex chemicals of high molecular weight which suggests that spider toxins offer few immediate opportunities for the chemical industry. However, the recent discovery of neurotoxins in venoms of orb-web spiders (Family Araneidue, Suborder Labidognatha) of low molecular weight (< 1 kDa) 1–4 has dramatically altered this perspective. These toxins are potent antagonists of transmitter receptors, which, because they seemingly exhibit a high specificity for quisqualate-sensitive l-glutamate receptors, are potentially attractive propositions as lead structures for pharmaceutical and pesticide industries.