Neural mechanisms mediating hypersecretion and motility patterns induced by enterotoxins

该项目旨在确定霍乱和其他引起腹泻的疾病所见的大量过量分泌水和盐的神经细胞。这些疾病中的许多都是通过特定的毒素起作用的，尽管这些毒素的生化目标已经被很好地了解了，但它们作用于的神经细胞从未被识别出来。此外，过度分泌与肠道推进活动大量增加的机制也尚不清楚。我们将使用豚鼠的小肠来研究这些问题，因为这种准备工作中的神经回路比其他任何准备工作都更好地了解。对三种已知通过不同机制激活神经系统的特定毒素做出反应的神经细胞将使用细胞内记录方法、标记染料注射和允许识别其神经化学的方法来确定。这将允许识别反应神经细胞的功能，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。

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.