Neural mechanisms mediating hypersecretion and motility patterns induced by enterotoxins

介导肠毒素诱导的分泌过多和运动模式的神经机制

• 批准号: nhmrc : 251504
• 负责人: Prof Joel Bornstein
• 金额: $ 27.69万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/neural-mechanisms-mediating-induced-enterotoxins/77617
• 关键词: Neural; mechanisms; mediating; hypersecretion; motility

This project aims to identify the nerve cells that are responsible for the massive oversecretion of water and salt seen with cholera and other diseases producing diarrhoea. Many of these disease act through specific toxins and, although the biochemical targets of these toxins are reasonably well understood, the nerve cells on which they act have never been identified. Furthermore, the mechanisms that couple the oversecretion with a massive increase in the propulsive activity of the intestine are also unknown. We will investigate each of these questions using the small intestine of the guinea-pig, because the nerve circuit in this preparation is better understood than that of any other. Nerve cells that respond to three specific toxins, each known to activate the nervous system via different mechanisms, will be determined using intracellular recording methods, injection of marker dyes and methods that allow the identification of their neurochemistry. This will allow the functions of responsive nerve cells to be identified and their places in the circuits that control secretion and propulsion to be determined. This information will be correlated with studies in whole animals being undertaken in Sweden so that potential sites for intervention can be identified.

该项目旨在确定导致霍乱和其他腹泻疾病中水和盐大量分泌过多的神经细胞。许多这些疾病通过特定的毒素起作用，尽管这些毒素的生化靶点已被相当清楚地了解，但它们作用的神经细胞从未被识别。此外，将分泌过多与肠道推进活动大量增加相结合的机制也是未知的。我们将使用豚鼠的小肠来研究这些问题，因为这种制剂中的神经回路比任何其他制剂都更容易理解。对三种特定毒素作出反应的神经细胞将使用细胞内记录方法、注射标记染料和允许识别其神经化学的方法来确定，每种毒素已知通过不同的机制激活神经系统。这将能够识别反应性神经细胞的功能，并确定它们在控制分泌和推进的回路中的位置。这些信息将与瑞典正在进行的整体动物研究相关联，以便确定潜在的干预地点。