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NEUROPEPTIDE CONTROL OF ENTERIC SPHINCTERS

肠括约肌的神经肽控制

基本信息

批准号：
3238583
负责人：
JAMES C REYNOLDS
金额：
$ 15.49万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1991-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3238583
关键词：
axon bombesin cats esophagogastric junction gastrointestinal motility /pressure histochemistry /cytochemistry immunochemistry laboratory rat neuropeptides pyloric region rectum /anus sympathetic ganglion sympathetic nervous system synapses vasoactive intestinal peptide

项目摘要

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.

肠神经系统介导括约肌反射，以及许多其他肠道功能。最内在的，肠神经含有肽类神经递质。我们的工作决定神经肽序列在下食管激活中的作用括约肌对酸的反应和幽门对肠腔内营养物质表明括约肌反射由神经肽的复杂相互作用介导。改变肽神经支配可能是导致肠道疾病的原因。能动性进一步定义的生理作用神经肽是有限的：缺乏研究，结构和功能;对神经肽之间的相互作用; 肽神经支配;缺乏特异性拮抗剂，肽递质本建议将审查肠神经系统控制下食管括约肌相关化学定义运动性反应的神经支配。具体来说，这些研究将把神经元的分布、突触模式和强度肽免疫反应性与括约肌对合成肽我们将继续研究肠神经之间，特别强调研究神经显示了突触相互作用的一致模式，免疫组织化学定位。二是地方肠神经的环路将使用逆行轴突运输标记物、霍乱毒素缀合物和凝集素。这些技术也将用于定义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，我们会继续研究近合成肽拮抗剂对血管收缩剂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支配影响（免疫学和手术诱导）对神经肽免疫反应性的影响。的肠神经细胞内完整性及其支持基质细胞将使用免疫组织化学来定义，神经丝和神经胶质丝。在每项研究中，通过免疫化学或形态测定法确定的特征将被与生理数据相关联，了解肠神经系统的回路，实现。