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.

线虫的运动系统是许多目前使用的驱虫剂的靶标，因为 运动行为的中断干扰了许多线虫在宿主内维持其位置的正常过程。遗传耐药性的问题使许多可用的药物不那么有效，因此重要的是开发新一代的抗耐药性药物。这项研究的目的是描述新的细胞间信号系统，这些系统在控制运动的运动神经系统中很重要。我们的策略是基于我们之前的工作，其中我们分离并测序了寄生线虫猪蛔虫中一个由29种新型内源性神经肽组成的大家族。初步实验表明，几乎所有测试的肽都具有有效的活性。 蛔虫系统有些会导致瘫痪，有些则会夸大运动。因此，神经肽在运动神经系统的整体活动中发挥着重要作用。有各种迹象表明，有更多的肽比我们已经分离到目前为止。没有迹象表明，目前可用的肽是最有效的，所以我们建议分离新的肽，集中在那些存在于运动神经系统，以检测新的肽，具有强大的生理活性。这是新一代驱虫药最终可以 开发