NEUROPEPTIDE CONTROL OF ENTERIC SPHINCTERS

肠道神经系统调节括约肌反射， 蠕动和许多其他肠道功能。最内在的、最具肠道感染力的 神经中含有多肽类神经递质。我们的工作决定了 食道下段激活中的神经肽序列 括约肌对酸的反应和幽门反应 管腔内营养物质表明，括约肌反射 由神经肽的复杂相互作用所介导。更改后的 肽类神经支配可能与肠道功能紊乱有关 能动性。对生理作用的进一步定义 神经肽受到以下因素的限制：缺乏相关研究 结构和功能；对 神经肽之间的相互作用；对 肽的神经支配；以及缺乏特异性的拮抗剂 多肽传递体。这项提案将审查 肠道神经系统在下食道控制中的作用 通过关联免疫组织化学定义的括约肌 运动性反应的神经支配。具体来说，这些研究 会将分布、突触模式和强度 多肽免疫反应性与括约肌反应 合成肽。我们将继续研究这些互动 肠神经之间的关系，特别强调研究神经 显示了co-2突触相互作用的一致模式 免疫组织化学定位。其次，本地化 肠神经的迂回将用逆行来定义。 轴突运输标记物，霍乱毒素结合物和凝集素。 这些技术还将用于通过以下方式定义LES神经支配 来自邻近器官和交感神经的肽能神经 神经节。第三，我们将继续审查敏感性和 近合成多肽拮抗剂对血管活性物质的特异性 肠多肽和蛙皮素。最后，我们将研究 慢性交感神经失神经的影响(免疫学 和手术诱导)对神经肽免疫反应性的影响。这个 肠神经的细胞内完整性及其支持 基质细胞将使用免疫组织化学方法定义 神经细丝和胶质细丝。在每项研究中，解剖学 通过免疫化学或形态测量确定的特征将是 与生理数据相关联，因此全面的 了解肠道神经系统的循环可以 才能实现。

The enteric nervous system mediates sphincteric reflexes, peristalsis and many other gut functions. Most intrinsic, enteric nerves contain peptide neurotransmitters. Our work determining neuropeptide sequences in the activation of the lower esophageal sphincter responses to acid and the pyloric responses to intraluminal nutrients suggests that Sphincteric reflexes are mediated by complex interactions of neuronpeptides. Altered peptide innervation may be responsible for disorders of intestinal motility. Further definition of the physiologic role for neuropeptides is limited by: the lack of studies that correlate structure and function; an inadequate understanding of the interactions between neuropeptides; an incomplete description of peptide innervation; and the lack of specific antagonists to peptide transmitters. This proposal will examine the role of the enteric nervous system in the control of the lower esophageal sphincter by correlating immunohistochemically-defined innervation with motility responses. Specifically, these studies will correlate the distribution, synaptic patterns and intensity of peptide immunoreactivity with the sphincteric responses to the synthetic peptides. We will continue to examine the interactions between enteric nerves, with special emphasis on studying nerves that show consistent patterns of synaptic interactions of co- localization by immunohistochemistry. Secondly, the local circuity of the enteric nerves will be defined using retrograde axonal transport markers, cholera toxin conjugates and lectinc. These techniques will also be used to define LES innervation by peptidergic nerves from adjacent organs and from sympathetic ganglia. Thirdly, we will continue to examine the sensitivity and specificity of nearly synthesized peptide antagonists to vasocative intestinal polypeptide and bombesin. Finally, we will examine the influence of chronic sympathetic denervation (immunologically and surgically induced) on neuropeptide immunoreactivity. The intracellular integrity of enteric nerves and their supporting stromal cells will be defined using immunohistochemistry of neurofilaments and glial filaments. In each study, anatomic features determined by immunochemistry or morphometry will be correlated with physiologic data so that a comprehensive understanding of the circuitary of the enteric nervous system can be achieved.