Potential roles of 5-hydroxytryptamine in diseases affecting the colon

该项目的总体目标是研究5-羟色胺（5-HT）在人类结肠中所起的生物学作用。5-羟色胺是一种天然存在的身体物质，通常参与控制许多身体活动。本项目的相关性在于5-HT过量或不足导致或促成某些临床状况的可能性。该项目的重点是慢性便秘、憩室病和肠易激综合征。令人关切的是，迄今为止，这些疾病还没有具体的治疗方法，因此该项目的主旨是增加这方面的知识，因此希望能开发出治疗方法。我们的药理学研究小组因其在定义药物对肠道的作用和描述其作用的靶点方面的经验而受到认可。这是通过使用综合方法实现的，其中不同的功能方法可靠地检测在肌肉层、供应它们的神经和使用实验动物的吸收表面的水平上的效果。此外，从废弃的手术材料中获得的分离的人类结肠碎片的使用已经成为该过程的宝贵内容。这使我们能够确定5-HT在结肠肌肉中具有靶位点，并且这导致正常自发收缩活动的松弛和抑制，据说在肠易激综合征患者中异常高。我们现在希望应用这些专业知识和知识来测试5-HT是否参与引起慢性便秘和憩室病，并设计一种药物，预计将在治疗肠易激综合征患者的价值。

The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and irritable bowel syndrome. It is a matter of concern that there are no specific treatments for these conditions to date, hence the thrust of the project is to increase knowledge in this area, so hopefully treatments will be developed. Our Pharmacology research group is recognised for its experience in defining drug effects on the intestine and in characterising the target sites on which they act. This has been achieved by using an integrated approach whereby different functional methods reliably detect effects at the levels of the muscle layers, the nerves that supply them and at the absorptive surface using experimental animals. In addition, the use of isolated pieces of human colon obtained from discarded operation material has been an invaluable inclusion into this process. This has allowed us to establish that 5-HT has a target site in the muscle of the colon and that this leads to relaxation and inhibition of the normal spontaneous contractile activity, said anecdotally to be abnormally high in patients with irritable bowel syndrome. We now wish to apply this expertise and knowledge to test whether 5-HT is involved in causing chronic constipation and diverticular disease and to design a drug that would be expected to be of value in treating patients with irritable bowel syndrome.