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

该项目涉及胃肠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，医疗服务的崩溃就会引起人们对霍乱和其他引起疾病的腹泻爆发的担忧，因此了解霍乱细菌引起腹泻的机制仍然是当务之急。众所周知，霍乱感染引起的腹泻是由一种肠毒素引起的，这种毒素通过肠壁产生大量过量分泌的水和盐，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，即肠道神经系统(ENS)。其他细菌毒素也有类似的作用，也需要ENS的活性才能体现这些作用。这个项目将确定这些毒素如何改变ENS的活动，以及它们对肠道运动的影响，这也是由ENS调节的。我们已经知道，水的运动和分泌是相互关联的，这种关系在一些更微妙的疾病中会受到干扰，比如肠易激综合征。这个项目将描述这种关系，从而揭示各种胃肠道疾病背后的生理学。

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.