Structure and Function of Ascaris Neuropeptides

蛔虫神经肽的结构和功能

• 批准号: 7268165
• 负责人: ANTONY O. STRETTON
• 金额: $ 0.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268165
• 关键词: Ascaris; anthelmintics; biological signal transduction; drug screening /evaluation; electrophysiology; high performance liquid chromatography; in situ hybridization; invertebrate locomotion; mass spectrometry; matrix assisted laser desorption ionization; molecular cloning; motor neurons; neuromuscular function; neuromuscular system; neuropeptides; neurophysiology; nucleic acid sequence; polymerase chain reaction; protein structure function; receptor binding; receptor coupling; tissue /cell culture; voltage /patch clamp

The locomotory system of nematodes is the target of many currently used anthelminthics, since disruption of locomotory behavior interferes with the normal processes by which many nematodes maintain their position within the host. The problem of genetic drug resistance is making many of the available drugs less effective, so it is important to develop new generations of anti-nematdde drugs. The proposed research aims to describe new intercellular signaling systems that are important in the motornervous system that controls locomotion. Our strategy is based on our previous work in which we isolated and sequenced a large family of 29 novel endogenous neuropeptides in the parasitic nematode, Ascaris suum. Preliminary experiments have shown that almost all of the peptides tested have potent activity .on the neuromuscular system of Ascaris. Some cause paralysis, others exaggerate locomotory movements. Neuropeptides, therefore, play an important role in the overall activity of the motornervous system. There is every indication that there are many more peptides than the ones we have isolated so far. There is no indication that the currently available peptides are the most potent, so we propose to isolate new peptides, concentrating on those that are present in the motornervous system, in order to detect new peptides that have potent physiological activity. This is basic research upon which new generations of anthelminthics can ultimately be developed.

线虫的机车系统是许多当前使用的驱动器的目标，因为 运动行为的破坏会干扰许多线虫在主机中保持其位置的正常过程。遗传耐药性的问题是使许多可用药物的效率降低，因此开发新一代的抗nematdde药物很重要。拟议的研究旨在描述在控制运动的整体系统中很重要的新的细胞间信号传导系统。我们的策略是基于我们以前的工作，在寄生虫suum中，我们隔离并测序了一个大型29个新型内源性神经肽。初步实验表明，几乎所有已测试的肽都具有有效的活性。 Ascaris系统。有些引起瘫痪，另一些则夸大了运动。因此，神经肽在整体系统的整体活性中起着重要作用。每种迹象都表明，肽比到目前为止隔离的肽还要多。没有迹象表明当前可用的肽是最有效的肽，因此我们建议分离新肽，集中于在整体系统中存在的肽，以检测具有有效生理活性的新肽。这是基础研究，新一代的驱星机构最终可以成为 发达。