Mechanisms of action of neurochemicals and modulators in human intestine: changes in disease

炎症性肠病（IBD）和特发性慢性便秘（ICC）是两种严重的胃肠道疾病，目前尚无有效的药物治疗方法。我们将调查在肠道中发现的神经化学物质异常导致这些疾病病因的假设。我们的研究将检查这些化学物质（神经紧张素和乙酰胆碱）在小肠和大肠中的作用部位（受体）。在动物肠道中，对这些化学物质反应的动力变化的控制机制已经得到了很好的研究，但在人类肠道中却很少有详细的信息。本研究将深入了解正常肠道的运作机制，为比较IBD或ICC患者肠道提供基础。我们还将研究急性憩室病（DD）手术切除的肠，这是另一种类型的炎症。对ICC患者结肠分离段的研究将确定肌肉的收缩性是普遍异常还是仅与所调查的化学物质有关。其他研究将调查肠道中发生的炎症过程，以及这在IBD中是否有所不同。我们的工作将有助于了解肠道在健康和胃肠道疾病中的功能，并可能导致IBD和ICC的新医学治疗。

Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in response to these chemicals have been well studied in animal intestine, but there is little detailed information from the human intestine. This study will provide insight into the mechanisms operating in the normal bowel, providing a base for comparing bowel obtained from patients with IBD or ICC. We will also study bowel removed at surgery for acute diverticular disease (DD), representing another type of inflammation. Studies on isolated segments of colon from ICC patients will determine whether the contractility of the muscle is abnormal in general or only with respect to the chemicals under investigation. Other studies will investigate the inflammatory processes occurring in the bowel and whether this differs in IBD. Our work will facilitate understanding of the function of the bowel in health and in gastrointestinal disorders and may lead to new medical treatments for IBD and ICC.