PHYSIOLOGICAL SYNERGISM BETWEEN CONOTOXINS

在上一个赠款期间，我们获得的证据表明， 捕食鱼类的锥螺的策略包括使用 毒品战略。所有的鱼狩猎锥螺干扰神经肌肉 通过使用靶向重要受体的多个肽的传递 和电动机电路（电动机组）中的离子通道。但不少 捕食芋螺的鱼类显然也有一套毒素， 毒液，elevening兴奋性休克的猎物，导致一个非常 快速的，僵硬的麻痹（闪电袭击阴谋集团）。 两个捕鱼的芋螺的雷击和马达阴谋 种，紫色芋螺和大芋螺进行了详细的分析， 并且所涉及的每种芋螺肽的药理学特异性将是 测定我们的数据表明，单个肽不仅会分化， 但是如果比较两种毒液，则可能靶向不同的位点。 我们已经提出了初步证据， 使用网络策略（而不是更常见的钩和线的方法 捕鱼）没有闪电袭击阴谋集团，而是 在发动机阴谋之前， 破坏神经肌肉传递。一组肽， 一般抑制感觉系统被假设属于 这可能有助于捕捉小鱼群的鱼， 一只蜗牛。在仙女阴谋集团中特别感兴趣的是 Conantokins，亚型特异性NMDA受体拮抗剂， 最近被证明是有效的抗惊厥药，具有高度的保护作用， 指数.因此，对属于 若虫阴谋集团可以提供新的工具， 神经系统

In the last grant period, we obtained evidence that the prey-capture strategy of fish-hunting cone snails involves the use of a combination drug strategy. All fish hunting cone snails interfere with neuromuscular transmission by using multiple peptides which target important receptors and ion channels in the motor circuitry (the motor cabal). However, many fish hunting Conus species apparently also have a set of toxins in their venom which elicits excitotoxic shock in the prey, resulting in a very rapid, rigid paralysis (the lightning-strike cabal). The lightning-strike and motor cabals of two fish-hunting Conus species, Conus purpurascens and Conus magus will be analyzed in detail, and the pharmacological specificity of each Conus peptide involved will be determined. Our data suggest that individual peptides not only diverge structurally but may target different sites if two venoms are compared. We have presented preliminary evidence that fish-hunting cone snails that use a net strategy (instead of the more common hook-and-line method for catching fish) do not have the lightning-strike cabal, but instead elicit anesthetic and sedative-like effects in prey before the motor cabal acts to disrupt neuromuscular transmission. The group of peptides which generally suppress sensory systems are hypothesized to belong to the nirvana cabal, which may facilitate capture of small schools of fish by a single snail. Of exceptional interest within the nirvana cabal are the conantokins, subtype-specific NMDA receptor antagonists which have recently been shown to be potent anticonvulsants with a high protective index. Thus, the characterization of the Conus peptides which belong to the nirvana cabal may provide novel tools for suppressing the activity of the nervous system.