ROLE OF GUT PEPTIDES IN INTESTINAL PERISTALSIS

肠肽在肠道蠕动中的作用

• 批准号: 3232511
• 负责人: John R Grider
• 金额: $ 12.15万
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232511
• 关键词: bombesin; cholecystokinin; colon; dogs; dynorphins; endorphins; enkephalins; gastrointestinal function; gastrointestinal hormones; gastrointestinal motility /pressure; guinea pigs; ileum; isoleucine; laboratory rat; neuromuscular function; neuropeptides; nicotinic receptors; somatostatin; stoichiometry; substance P; vasoactive intestinal peptide

The aim of this application is to examine the participation of myenteric neuropeptides in the regulation of an integrated neuromuscular function: the intestinal peristaltic reflex. Initial work focused on the identification of vasoactive intestinal peptide (VIP) and its cosynthesized, coreleased homolog, peptide histidine isoleucine (PHI) as the neurotransmitters responsible for neurally- induced relaxation. The stoichiometry of VIP release and muscle relaxation was established and the existence of presynaptic inhibitory autoreceptors regulating release of VIP/PHI was demonstrated. VIP/PHI neurons were shown to be tonically active and to mediate the dominant inhibitory neural tone that normally masks myogenic phasic activity. A preparation was devised that enabled separate measurement of the components of the peristaltic reflex (ascending contraction and descending relaxation) and identification of peptide and non-peptide neurotransmitters released with each component. The identification was made possible by the use of specific antisera and is being confirmed by use of selective peptide antagonists of VIP, tachykinin, GRP/bombesin, CCK and opioid peptide receptors. The modulatory influence of somatostatin and opioid neurons on VIP/PHI neurons- the mediators of descending relaxation- is being investigated. Somatostatin neurons act as facilitatory interneurons in descending pathways whereas opioid neurons appear to act as restrictive neurons: the two types of neurons modulate release of VIP/PHI in opposite directions. These studies are being extended to other myenteric neuropeptides (CCK, GRP/bombesin, substance P and galanin) to determine the mechanism of release and the reciprocal influence each has on its own release (autoregulation) and the release of other peptides. The approach will be facilitated by the use of dispersed myenteric ganglia immobilized in Biogel and perfused in minichambers. An important advance is the development of a flat sheet muscle preparation which enables measurement of the components of the peristaltic reflex in human intestinal muscle tissue obtained at surgery. Preliminary studies have demonstrated the versatility of this preparation and its usefulness in identifying the neurotransmitters involved in the regulation of the peristaltic reflex in humans. The identification of neurotransmitters is made increasingly possible by the availability of specific antisera for immunoneutralization and immunoassay and of selective peptide antagonists, including antagonists presently available for VIP, CCK, tachykinins/bombesin and opioid peptides.

该应用的目的是检查 在整合的调节中，骨膜神经肽 神经肌肉功能：肠蠕动反射。 最初的 侧重于鉴定血管活性肠肽的工作 （VIP）及其合成的，共发行的同源性，肽组氨酸 异亮氨酸（PHI）作为负责神经递质的神经递质 诱导的放松。 VIP释放和肌肉的化学计量法 建立了放松，并存在突触前的 调节VIP/PHI释放的抑制自身受体 证明。 VIP/PHI神经元显示具有色调活性 并调解通常通常 掩盖肌源性阶段活性。 设计了一项准备工作 启用了对组件的单独测量 蠕动反射（上升收缩和下降 放松）和肽和非肽的鉴定 神经递质与每个组件释放。 这 使用特定的抗血清使识别成为可能 并通过使用选择性肽拮抗剂来确认 VIP，旋转金，GRP/bombesin，CCK和阿片类肽 受体。 生长抑素和阿片类药物的调节作用 VIP/PHI神经元上的神经元 - 下降的介体 放松 - 正在研究。 生长抑素神经元充当 降低途径的促进性中间神经元，而阿片类药物 神经元似乎充当限制性神经元：两种类型的 神经元在相反的方向上调节VIP/PHI的释放。 这些研究已扩展到其他肌肉 神经肽（CCK，GRP/Bombesin，物质P和Galanin）至 确定释放的机理和相互影响 每个都有自己的释放（自动调节）和释放 其他肽。 该方法将通过使用 分散了固定在biogel中并灌注的肌植物神经节 Minichambers。 一个重要的进步是开发公寓 板肌肉制备能够测量 人肠肌肉中蠕动反射的成分 在手术时获得的组织。 初步研究 证明了这种制剂的多功能性及其有用性 在确定与调节有关的神经递质 人类的蠕动反射。 识别 通过可用性使神经递质变得越来越成为可能 特定的抗血清进行免疫中和化和免疫测定 和选择性肽拮抗剂，包括拮抗剂 目前可用于VIP，CCK，tachykinins/bombesin和阿片类药物 肽。