ENTERIC NEURAL CONTROL OF COLON

肠兴奋性和抑制性运动神经元都重要地 有助于调节结肠动力，并且是结肠动力的核心。 的过程。拟议的实验将研究如何 这些运动神经元调节正在进行的电和收缩， 活动发生在狗和人的环形肌肉层 结肠通过使用各种拮抗剂，我们将表征电 和与以下相关的收缩事件：I.胆碱能兴奋性神经元 答案，二。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乙酰胆碱和速激肽 (TK)两者都有助于兴奋性神经反应，NO，VIP和 ATP都参与抑制性神经反应。的直接证据 TK和VIP的放行将通过放行研究提供。以来 环形肌层功能复杂，完整的 层将与此层的子部分进行比较，子部分包含 单个起搏器/神经丛区域或没有神经丛/起搏器区域。在这 我们将确定肠神经元功能性 支配各个子部分，并量化它们的方式， 调节这些区域的机械和电活动。这 信息将被用来构建一个模型， 抑制性运动神经元调节完整的环 肌肉层我们假设兴奋性和抑制性运动 神经元在功能上支配心脏的起搏区和非起搏区， 环形肌肉层和运动神经元的净效应 结肠能动性是电和机械变化的总和， 它们在起搏器和非起搏器区域中产生。而 人们对犬科动物的电和收缩特性了解很多 结肠，我们对人类肌肉的了解还不完全。通过比较 因此，我们不仅可以提高我们的 人类肌肉的知识，而且还提供了一种评估 犬结肠作为人类结肠模型的有用程度 功能更详细地了解结肠的正常生理学 也可以提供重要的信息，以改善这些条件， 肠易激综合征和先天性巨结肠症， 为更常见的疾病开发新疗法， 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.