ROLE OF GUT PEPTIDES IN INTESTINAL PERISTALSIS

肠肽在肠道蠕动中的作用

• 批准号: 3447283
• 负责人: John R Grider
• 金额: $ 5.58万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447283
• 关键词: colon; gastrointestinal function; ileum; naloxone; peptides; somatostatin; vasoactive intestinal peptide

The aim of this proposal is to examine the role of peptidergic neurons of the myenteric plexus in the regulation of small intestinal and colonic peristalsis in the guinea pig and rabbit. The activity of neurons containing vasoactive intestinal peptide (VIP), enkephalin, dynorphin and somatostatin, and their interaction with each other and with regulatory cholinergic interneurons will be examined using vascularly perfused ileal and colonic segments that permit vascular sampling orad and caudad to central distension stimulus. Peptide release will also be examined in muscle strips containing intact myenteric plexus or severed axonal projections. JA model of peristalsis based on the topography of peptidergic neurons in the myenteric plexus and circular muscle is proposed to serve as a basis for experimental analysis. The main components of the model as they relate to peptidergic neurons are as follows: 1. VIP neurons projecting caudad into myenteric plexus and circular muscle are the mediators of aboral relaxation during peristalsis; 2. Enkephalin/dynorphin neurons projecting orad into myenteric plexus and caudad into circular muscle regulate the activity of VIP neurons, acting chiefly to inactivate these inhibitory neurons; 3. Somatostatin neurons projecting caudad within the myenteric plexus but not into circular muscle act as facilitatory interneurons that intensify the activity of VIP neurons; and 4. These peptidergic neurons receive input from a network of cholinergic interneurons via nicotinic and possibly muscarinic M1 ganglionic receptors. The participation of these peptidergic neurons will be identified by : 1. measurement of peptide release during peristalsis from whole segments as well as from segments orad and caudad to a central distension stimulus; 2. measurement of peristaltic activity in the presence of specific antagonists and antisera (naloxone and Mr2266 for enkephalin and dynorphin neurons, VIP and somatostatin antisera, and the selective M1 and M2 muscarinic antagonists, pirenzepine and 4-DAMP); and 3. Measurement of peptide release from isolated muscle strips with intact myenteric plexus or severed axonal projections. The approach described in the present proposal is an attempt to study the role of peptidergic neurons in the regulation of an important motor function of the gut.

该提议的目的是检查肽能神经元的作用 小肠和结肠调节中的脑丛 豚鼠和兔子中的蠕动。 神经元的活性 含有血管活性肠肽（VIP），Enkephalin，dynorphin和 生长抑素，彼此之间的相互作用以及调节 胆碱能中间神经元将使用血管灌注的回肠检查 以及允许血管采样Orad和Caudad的结肠段 中央延伸刺激。 肽释放也将在 包含完整肌丛或切断的轴突的肌肉条 预测。 基于肽神经元的地形的蠕动的JA模型 提议肌丛和圆形肌肉作为基础 用于实验分析。 模型相关的主要组成部分 对肽性神经元的神经元如下：1。VIP神经元投射caudad 进入肌丛和圆形肌肉是原住民的介体 蠕动期间放松； 2。Enkephalin/dynorphin神经元投影 Orad进入肌神经丛，并进入圆形肌肉调节圆形肌肉 VIP神经元的活性主要使这些抑制作用灭活 神经元； 3。生长抑素神经元在肌室内投射caudad 神经丛，而不是圆形肌肉作为促进性中间神经元的作用 增强VIP神经元的活性；和4。这些肽能神经元 通过烟碱从胆碱能中间神经元网络接收输入 可能是毒蕈碱M1神经节受体。 这些肽基神经元的参与将通过：1。 从整个细分市场的蠕动期间肽释放的测量 以及从奥拉德（Orad）和库达（Caudad）段到中央延伸刺激； 2。 在存在特定拮抗剂的情况下测量蠕动活性 和Antisera（用于Enkephalin和Dynorphin神经元的Naloxone和MR2266，VIP 以及生长抑素抗血清，以及选择性M1和M2毒蕈碱 拮抗剂，吡renzepine和4-damp）；和3。测量肽释放 从完整的肌丛或切断的轴突的孤立肌肉条中 预测。 本提案中描述的方法是尝试研究 肽能神经元在重要电动机调节中的作用 肠的功能。