ENTERIC NEURAL CONTROL OF COLON

肠兴奋性运动神经元和抑制性运动神经元都很重要 有助于调节结肠运动，并且是 蠕动过程。拟议中的实验将调查如何 这些运动神经元调节正在进行的电和收缩 发生在狗和人的环状肌层的活动 冒号。通过使用不同的拮抗剂，我们将表征电学 以及与以下相关的收缩事件：I.胆碱能兴奋性神经元 反应，II.抑制性神经元反应和III.非胆碱能 兴奋性神经元反应。我们假设ACh和速激肽 (TK)均参与兴奋性神经反应，NO、VIP和 三磷酸腺苷都有助于抑制神经反应。的直接证据 TKS的发布，VIP将从发布研究中提供。自.以来 环肌层功能复杂，节段性完好 图层将与包含以下任一项的该图层的子部分进行比较 单个起搏器/丛区域或无丛/起搏器区域。在这 我们将确定肠道神经元在多大程度上功能 灌输不同的小节，并量化它们 调节这些区域的机械和电气活动。这 信息将被用来构建一个模型，说明如何兴奋和 抑制性运动神经元调节完整环的活动 肌肉层。我们假设兴奋性和抑制性运动 起搏区和非起搏区的神经元都有功能支配 环肌层和运动神经元的净效应 结肠运动是电和机械变化的总和， 它们既在起搏器区域也在非起搏器区域产生。而当 很多人都知道犬类的电学和收缩特性。 结肠，我们对人类肌肉的知识还不够完整。通过比较 在这两个物种中的反应，因此我们不仅将增强我们的 对人类肌肉的了解，也提供了一种评估 犬结肠是人类结肠的有用模型的程度 功能。更详细地了解结肠的正常生理学 还可以提供重要信息，以改善以下条件 肠易激综合征和先天性巨结肠症 针对更常见疾病的新疗法的开发，如 便秘和腹泻。

Enteric excitatory and inhibitory motor neurons both importantly contribute to modulation of colonic motility and are central to the process of peristalsis. The proposed experiments will investigate how these motor neurons modulate the ongoing electrical and contractile activity which occurs in the circular muscle layer of the dog and human colon. By using various antagonists we will characterize the electrical and contractile events associated with: I. Cholinergic excitatory neuronal responses, II. Inhibitory neuronal responses and III. Non-cholinergic excitatory neuronal responses. We hypothesize that ACh and tachykinins (TK) both contribute to excitatory neural responses and that NO, VIP and ATP all contribute to inhibitory neural responses. Direct evidence for release of TKs, and VIP will be provided from release studies. Since the circular muscle layer is functionally complex, segments of the intact layer will be compared to subsections of this layer which contain either a single pacemaker/plexus region or no plexus/pacemaker region. In this way we will determine the extent to which enteric neurons functionally innervate the various subsections and quantitate the manner which they modulate mechanical and electrical activity in these regions. This information will be used to construct a model of how excitatory and inhibitory motor neurons modulate the activity of the intact circular muscle layer. We hypothesize that both excitatory and inhibitory motor neurons functionally innervate both pacemaker and non-pacemaker regions of the circular muscle layer and that the net effect of motor neurons on colonic motility is the sum of the electrical and mechanical changes which they produce in both pacemaker as well as non-pacemaker regions. While much is known of the electrical and contractile properties of the canine colon, our knowledge of the human muscle is less complete. By comparing responses in these two species we will therefore not only enhance our knowledge of the human muscle but also provide a means for assessing the degree to which the canine colon is a useful model for human colonic function. Understanding in more detail the norma physiology of the colon may also provide important information to improve such conditions as irritable bowel syndrome and Hirschsprung's disease as well as aiding in the development of new treatment for more common maladies such as constipation and diarrhea.