Neuropharmacological Studies of a Parasitic Nematode

寄生线虫的神经药理学研究

• 批准号: 6415759
• 负责人: RALPH E DAVIS
• 金额: $ 13.78万
• 依托单位: NORTHWESTERN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415759
• 关键词: Ascaris; GABA receptor; anthelmintics; electrophysiology; evoked potentials; gamma aminobutyrate; immunocytochemistry; invertebrate locomotion; membrane potentials; membrane transport proteins; motor neurons; neural transmission; neurons; neuropharmacology; neurotransmitter antagonist; synapses

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.

描述：寄生线虫是世界上最普遍的 致病微生物控制它们在很大程度上取决于 针对运动系统的抗寄生虫药物，因为运动是 这是许多寄生线虫维持其在体内位置所必需的 主持人不幸的是，驱虫药的抗药性已经影响了 许多抗寄生虫药物，有必要完善这些药物和/或 寻找新的。 拟议的研究将使用电生理技术来研究 主要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。相比 以前的工作集中在肌肉上，这项研究的目的是 阐明线虫神经系统的GABA药理学，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，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 和运输机。将研究GABA受体的药理学 选择性激动剂和拮抗剂，以表征 运动神经系统中的GABA反应。同样，GABA的药理学 转运蛋白将与底物和抑制剂一起探索，以表征 运输机因为神经系统最终负责 行为控制，任何这些GABA相关的药物，损害正常的 神经系统的功能也可能会破坏运动。上 根据这些研究，目前使用的唯一GABA相关驱虫药 （哌嗪）可以被精炼，并且可以发现新的抗寄生虫药物。