Neuropharmacological Studies of a Parasitic Nematode

描述：寄生线虫是世界上最流行的线虫之一 致病生物体。控制它们在很大程度上依赖于 针对运动系统的抗寄生虫药物，因为运动是 对于许多寄生线虫来说，维持它们在 主持人。不幸的是，驱虫药的抗药性已经影响了疗效。 在许多抗寄生虫药物中，有必要对这些药物和/或 寻找新的目标。 这项拟议的研究将使用电生理技术来研究 大鼠初级抑制性神经递质系统的神经药理学 线虫，GABA(γ-氨基丁酸)信号系统。与之形成鲜明对比的是 以前的工作都集中在肌肉上，这次研究的目的是 阐明线虫神经系统的GABA药理，特别是 运动神经系统中控制运动行为的运动神经元。 这项工作将利用寄生线虫猪蛔虫，这是一个模型系统 研究线虫神经生理学。GABA信号系统由受体组成 和传送器。GABA受体的药理学将用 选择性激动剂和拮抗剂用于表征潜在的受体 运动神经系统中的GABA反应。同样，GABA的药理作用 转运蛋白将用底物和抑制剂进行探索，以表征 传送器。因为神经系统最终要对 对行为的控制，任何这些与GABA相关的药物都会损害正常的 神经系统的功能也可能扰乱运动。论 根据这些研究，目前使用的唯一与GABA相关的驱虫药 (哌嗪)可能会被提炼，可能会发现新的抗寄生虫药物。

DESCRIPTION: Parasitic nematodes are among the world's most prevalent disease-causing organisms. Controlling them has largely depended on anti-parasite drugs that target the locomotory system, since locomotion is necessary for many parasitic nematodes to maintain their position within the host. Unfortunately, anthelmintic resistance has compromised the effectiveness of many antiparasite drugs, necessitating the refinement of these drugs and/or the search for new ones. The proposed research will use electrophysiological techniques to study the neuropharmacology of the primary inhibitory neurotransmitter system in nematodes, the GABA (gamma-aminobutyric acid) signaling system. In contrast to previous work that has focused on muscle, the aim of this research is to elucidate the GABA pharmacology of the nematode nervous system, specifically the motorneurons of the mOtornervous sytem which control locomotory behavior. This work will make use of the parasitic nematode Ascaris suum, a model system for nematode neurophysiology. The GABA signaling system consists of receptors and transporters. The pharmacology of GABA receptors will be studied with selective agonists and antagonists to characterize the receptors underlying GABA responses in the motornervous system. Likewise, the pharmacology of GABA transporters will be explored with substrates and inhibitors to characterize the transporters. Since the nervous system is ultimately responsible for control of behavior, any of these GABA-related drugs that compromise the normal function of the nervous system are likely to also disrupt locomotion. On the basis of these studies, the sole GABA-related anthelmintic currently in use (piperazine) may be refined and new anti-parasite drugs may be discovered.