ROLE OF GUT PEPTIDES IN INTESTINAL PERISTALSIS

肠肽在肠道蠕动中的作用

• 批准号: 3232512
• 负责人: John R Grider
• 金额: $ 16.65万
• 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 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232512
• 关键词: GABA receptor; bombesin; calcitonin gene related peptide; cholecystokinin; cholinergic receptors; colon; cytosine arabinoside; floxuridine; gamma aminobutyrate; gastrointestinal function; gastrointestinal hormones; gastrointestinal motility /pressure; guinea pigs; hormone regulation /control mechanism; interneurons; intestinal mucosa; isoleucine; jejunum; laboratory rat; ligands; muscarinic receptor; myenteric plexus; neural information processing; neuromuscular function; neurotransmitter receptor; neurotrophic factors; nicotinic receptors; peptides; radioimmunoassay; serotonin; serotonin receptor; somatostatin; tachykinin; vasoactive intestinal peptide; veratrum alkaloid

The aim of this proposal is to characterize the neural pathways that regulate the intestinal peristaltic reflex in humans and animals, in particular, to identify the peptide transmitters that control the sensory, modulatory and motor limbs of the reflex. We have devised techniques to measure the sensory and motor limbs of the reflex and neuropeptide release associated with each, and have used various probes (specific antisera and peptide antagonists, axonal and sensory neurotoxins and peptide immunoassay and receptor-specific bioassay) to establish the functional coupling between myenteric neuropeptides and each component of the reflex. We have also devised three preparations that provide complementary information: isolated myenteric ganglia to examine the interplay between neurons that project within the plexus (interneurons); muscle strips with axonal remnants only to examine the interplay between neurons that project into circular muscle; and cultures of neurons derived from isolated myenteric ganglia: this unique system permits predominant or exclusive expression of one neuropeptide, and thus, identifies the singular effects of myenteric peptides on release of the expressed peptide. Thus far, we have shown that VIP/PHI motor neurons mediate descending relaxation, and cholinergic and tachykinin (SP/SK) motor neurons mediate ascending contraction. We have also shown that opioid and somatostatin neurons act as modulatory neurons to enhance or restrain the activity of VIP neurons. In addition, we have obtained evidence from isolated ganglia for the existence of a feedback mechanism between somatostatin and VIP that would enable a segment to switch from relaxation to contraction during peristalsis. We now propose to examine the participation of other myenteric transmitters in the regulation of the peristaltic reflex. Preliminary studies using the preparations listed above, show that these transmitters exert precise modulatory effects on sensory and motor limbs of the reflex: somatostatin as a facilitatory neuropeptide acting via inhibition of opioid peptides; galanin as postjunctional synergist in descending pathways; GRP, CCK and NPY as prejunctional stimulatory or inhibitory modulators; GABA as stimulatory prejunctional modulator in ascending and descending pathways; serotonin, depending on receptor type, as prejunctional inhibitory or stimulatory modulator; and CGRP as sensory mediator. The approach has provided the first characterization of the peptide transmitters that regulate the peristaltic reflex in humans and animals.

该提议的目的是表征神经途径 调节人类和动物的肠蠕动反射， 特别是要识别控制感觉的肽发射器， 反射的调节和运动四肢。 我们已经将技术设计为 测量反射和神经肽释放的感觉和运动四肢 与每个相关联，并使用了各种探针（特定的抗血清和 肽拮抗剂，轴突和感觉神经毒素以及肽免疫测定 和受体特异性生物测定）以建立功能耦合 在骨膜神经肽和反射的每个成分之间。 我们有 还设计了三个提供互补信息的准备工作： 孤立的myenteric神经节检查了神经元之间的相互作用 丛中的项目（中间神经元）；肌肉条带有轴突 残余只是检查将投射到的神经元之间的相互作用 圆形肌肉；以及来自孤立的myenteric的神经元培养 神经节：这个独特的系统允许主要或独家表达 一种神经肽，因此鉴定了肌植物的奇异作用 释放表达肽的肽。 到目前为止，我们已经表明VIP/PHI运动神经元介导了下降 放松，胆碱能和速素（SP/SK）运动神经元介导 上升收缩。 我们还表明阿片类药物和生长抑素 神经元充当调节性神经元，以增强或限制活性 VIP神经元。 此外，我们从孤立的神经节中获得了证据 对于生长抑素和VIP之间存在反馈机制 可以使一个细分市场从放松转变为收缩 蠕动。 我们现在建议研究其他肌发射机的参与 在蠕动反射的调节中。 初步研究 上面列出的准备工作，表明这些发射机施加精确的 对反射的感觉和运动四肢的调节作用：生长抑素 作为通过抑制阿片类肽作用的促进性神经肽； Galanin作为后途径的后术协同作用； GRP，CCK和 npy作为持续的刺激或抑制调节剂； gaba as 在上升和下降途径中的刺激性诊断调节器； 5-羟色胺，具体取决于受体类型，作为抑制性抑制或 刺激调节器；和CGRP作为感官中介。 方法有 提供了肽发射机的第一个表征 调节人和动物的蠕动反射。