Neural coordination of intestinal motility and mucosal secretion of water and salt - role in toxin induced diarrhoea

该项目涉及胃肠道功能紊乱的一些基本机制，特别是引起腹泻的机制。每当发生自然灾害（例如最近的海啸）或战争时，医疗服务的中断都会引起人们对霍乱和其他腹泻病爆发的担忧，因此了解霍乱细菌引起腹泻的机制仍然是一项重要任务。众所周知，霍乱感染引起的腹泻是由肠毒素引起的，肠毒素的作用是通过肠壁产生大量的水和盐的过度分泌，如果不加以控制，就会因脱水而死亡。这种效应需要肠壁内神经细胞的活动，即肠神经系统（ENS）。其他细菌毒素具有类似的作用，并且也需要ENS的活性来表现这些作用。该项目将确定这些毒素如何改变ENS的活性，以及它们对肠道运动的影响，肠道运动也受到ENS的调节。我们已经知道，运动和水的分泌是相互关联的，这种关系在一些更微妙的疾病中受到干扰，如肠易激综合征。本项目将阐明这种关系，从而阐明各种胃肠道疾病的生理学基础。

This project deals with some of the basic mechanisms underlying disorders of gastrointestinal function and in particular with the mechanisms responsible for diarrhoea. Whenever there is a natural disaster (the recent tsunami for example) or a war, the breakdown of medical services leads to concern about outbreaks of cholera and other diarrhoea causing diseases, so understanding the mechanisms by which the cholera bacterium cause diarrhoea remains a major imperative. It is known that the diarrhoea resulting from cholera infection is produced by an enterotoxin, which acts to produce a massive over-secretion of water and salt through the intestinal wall, which if it is not controlled causes death by dehydration. This effect requires the activity of the nerve cells within the gut wall, the enteric nervous system (ENS). Other bacterial toxins have similar effects and also require activity of the ENS for these effects to be manifested. This project will identify how these toxins alter the activity of the ENS and the effects that they have on intestinal movements which are also regulated by the ENS. We already know that the movements and secretion of water are related to each other and that this relationship is disturbed in some more subtle diseases like irritable bowel syndrome. This project will characterise this relationship, thereby shedding light on the physiology underlying a variety of gastrointestinal disorders.