The Role of Intestinal Mucosal Serotonin Uptake in IBS

肠粘膜血清素摄取在 IBS 中的作用

• 批准号: 6998348
• 负责人: MATTHEW D COATES
• 金额: $ 1.31万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-29 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998348
• 关键词: biological signal transduction; biopsy; clinical research; gastrointestinal motility /pressure; gene induction /repression; genetically modified animals; human subject; intestinal mucosa; irritable bowel syndrome; laboratory mouse; messenger RNA; molecular pathology; neurotransmitter transport; paroxetine; predoctoral investigator; serotonin; serotonin transporter

DESCRIPTION (provided by applicant): Serotonin (5-HT) is a key neurotransmitter and signaling molecule in the gut. 5-HT release from enterochromaffin cells residing within the intestinal mucosa results in transduction of luminal stimuli initiating peristaltic, secretory and nociceptive reflexes. The serotonin-selective reuptake transporter (SERT), which is expressed on intestinal enterocytes, terminates the actions of 5-HT by removing it from the interstitial space. Disruption of these actions could lead to altered serotonergic signaling and potential gastrointestinal dysfunction. The role of the 5-HT in IBS remains unclear, but our recent data suggest distinct changes of 5- HT availability exist in individuals with this disorder. We have demonstrated that individuals with IBS have decreased levels of SERT while maintaining levels of 5-HT release comparable to those of healthy controls. It is possible that diminished uptake could allow 5-HT to persist within the interstitium longer than normal, causing overstimulation of the serotonergic reflexes noted above. The overall hypothesis to be tested by these proposed studies is that intestinal 5-HT availability is increased in IBS due to decreased expression of SERT, and that resultant changes in 5-HT signaling contribute to altered gut function in IBS.

描述（由申请人提供）： 5-羟色胺（5-HT）是肠道中的关键神经递质和信号分子。 5-HT从肠粘膜内的肠球毒细胞中释放，导致腔刺激的转导，引发蠕动，分泌和伤害感受反射。在肠肠上皮细胞上表达的血清素选择性转运蛋白转运蛋白转运蛋白（SERT）通过将其从间质空间中删除来终止5-HT的作用。这些动作的破坏可能导致血清素能信号传导改变和潜在的胃肠道功能障碍。 5-HT在IBS中的作用尚不清楚，但是我们最近的数据表明，这种疾病的个体中存在5-HT可用性的明显变化。我们已经证明，IBS患者的SERT水平降低，同时保持5-HT释放的水平，可与健康对照相媲美。摄取的摄取减少可能使5-HT在间质中的持续时间比正常情况更长，从而导致上面提到的血清素能反射过度刺激。这些提出的研究要检验的总体假设是，由于SERT的表达降低，IBS的肠道5-HT可用性增加，并且5-HT信号的结果变化会导致IBS中的肠道功能改变。