The Neural Control of Serotonin Release from Intestinal Enterochromaffin (EC) Cells

许多功能性胃肠问题被认为是由肠壁内神经的正常功能中断引起的。这些神经被认为是从肠道内壁的一类特殊细胞（称为肠嗜铬细胞）接收有关肠内容物的信息。肠嗜铬细胞通过调节递质血清素的释放来完成这项工作。在某些疾病中，如肠易激综合征（IBS），它可以影响上肠和下肠，血清素携带的信息可能会变得混乱。因此，控制从肠内分泌细胞释放5-羟色胺是理解健康和疾病的重要过程。我们将直接在豚鼠小肠和大肠以及人大肠的分离组织中研究这种释放。本研究将探讨5-羟色胺的作用及其从肠嗜铬细胞释放的调节。5-羟色胺释放的问题可能是疾病的基础，因此，了解这种释放是如何控制的将为针对5-羟色胺释放的通道或受体的新的和特定的治疗提供基础。这些数据可能有助于开发治疗胃肠道问题，如肠易激综合征，慢性假性肠梗阻和胃食管反流病。血清素的释放也与霍乱和抗癌治疗相关的腹泻密切相关。这项拟议的研究将有助于正在进行的阻断神经末梢上5-羟色胺受体的特定疗法的开发，并将导致通过调节5-羟色胺的释放来补充现有疗法的新疗法。

Many functional gastrointestinal problems are believed to be caused by a disruption of the normal functioning of the nerves within the wall of the gut. These nerves are believed to receive information about the contents of the intestine from a specialised class of cell lining the inside wall of the gut called the enterochromaffin cell. The enterochromaffin cell does this job by modulating the release of the transmitter serotonin. In some disorders, like the Irritable Bowel Syndrome (IBS) which can affect the upper and lower intestine, the information that serotonin carries can become confused. Thus, the control of the release of serotonin from the enteroendocrine cell is an important process to understand in health and in disease. We will investigate this release directly in isolated tissues from guinea pig small and large intestine and from human large intestine. This study will examine the role of serotonin and the modulation of its release from the enterochromaffin cell. Problems with serotonin release may underlie disease, thus, understanding how this release is controlled will provide a foundation for new and specific therapies that target channels or receptors specific to the release of serotonin. These data could help to develop therapies for gastrointestinal problems such as the IBS, chronic intestinal pseudo-obstruction and gastro-oesophageal reflux disease. The release of serotonin is also intimately linked with the diarrhea associated with cholera and anti-cancer treatments. The proposed study will contribute to the ongoing development of specific therapies that block serotonin receptors on the nerve terminal and will lead to new therapies that compliment existing therapies by modulating the release of serotonin.