Potential roles of 5-hydroxytryptamine in diseases affecting the colon

5-羟色胺在结肠疾病中的潜在作用

• 批准号: nhmrc : 143509
• 负责人: A/Pr Ian Coupar
• 金额: $ 23.07万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/potential-roles-5-affecting-colon/99774
• 关键词: Potential; roles; hydroxytryptamine; diseases; affecting

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.

该项目的总体目标是研究 5-羟色胺 (5-HT) 在人类结肠中发挥的生物学作用。 5-HT 是体内天然存在的物质，通常参与控制许多身体活动。该项目的相关性在于 5-HT 可能因过量或缺乏而导致或促成某些临床病症。该项目重点关注的疾病是慢性便秘、憩室病和肠易激综合征。令人担忧的是，迄今为止还没有针对这些病症的具体治疗方法，因此该项目的主旨是增加这方面的知识，因此希望能够开发出治疗方法。我们的药理学研究小组因其在定义药物对肠道的作用以及表征药物作用的靶位点方面的经验而受到认可。这是通过使用一种综合方法来实现的，其中不同的功能方法可以使用实验动物可靠地检测肌肉层、供应肌肉的神经以及吸收表面的效果。此外，使用从废弃的手术材料中获得的分离的人类结肠碎片已成为这一过程的宝贵内容。这使我们能够确定 5-HT 在结肠肌肉中有一个目标位点，这会导致正常自发收缩活动的松弛和抑制，据说肠易激综合征患者的 5-HT 水平异常高。我们现在希望应用这些专业知识和知识来测试 5-HT 是否与引起慢性便秘和憩室病有关，并设计一种有望对治疗肠易激综合征患者有价值的药物。