GUT PEPTIDES AND INTESTINAL PERISTALSIS

肠肽和肠道蠕动

• 批准号: 2518265
• 负责人: John R Grider
• 金额: $ 20.67万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518265
• 关键词: cholecystokinin; gamma aminobutyrate; gastrointestinal function; gastrointestinal hormones; gastrointestinal motility /pressure; guinea pigs; hormone regulation /control mechanism; human tissue; laboratory rabbit; laboratory rat; myenteric plexus; neural information processing; neuroendocrine system; neuromuscular function; neuropeptides; neurotransmitter receptor; serotonin; smooth muscle; somatic reflex; somatostatin; tachykinin; vasoactive intestinal peptide

The objective of this proposal is to identify the direct measurement the enteric sensory, modulatory and motor neurotransmitters that regulate athe peristaltic reflex elicited by muscle stretch and mucosal stimulation in rat colon and human intestine. Our previous studies and preliminary experiments have led us to identify neuronal circuits consisting of modulatory neurons coupled to motor neurons that account for reciprocal circular and longitudinal muscle activity during the ascending and descending phases of the reflex. The experimental approach exploits novel preparations that enable identification of various components of the circuits: (i) flat-sheet compartmented intestinal segments with which to measure specifically the release of sensory transmitters; (ii) longitudinal muscle strips with adherent myenteric plexus with which to identify the coupling of modulatory neurons to motor neurons innervating longitudinal muscle; (iii) circular muscle st rips devoid of myenteric plexus with which to measure presynaptic regulation of transmitter release, and from which to prepare synaptosomes to characterize the binding of transmitters to presynaptic receptors; and (iv) freshly dispersed myenteric ganglia with which to examine feedback regulation of modulatory interneurons within the plexus. In Specific Aim I, studies in rat colonic and human intestinal segments will identify (a) the role of an integrated modulatory circuit consisting of somatostatin, enkephalin and GABA neurons that regulates motor neurons innervating circular and longitudinal muscle during the ascending and descending phases of the reflex, and (b) the role of 5-HT acting via neuronal 5-HT4 receptors in regulating release of the sensory transmitters, CGRP and the tachykinins, substance P (SP) and neurokinin A (NKA). In Specific Aim II, studies in myenteric plexus-longitudinal muscle strips will demonstrate that the modulatory circuit acts via VIP/PACAP/NOS neurons to regulate cholinergic/tachykinin motor neurons that innervate longitudinal muscle. In Specific Aim III, studies on circular muscle strips containing only axonal terminals will identify the presence of regulatory presynaptic (i.e., axo-axonal) interactions between modulatory nerve terminals and excitatory and inhibitory motor nerve terminals. The existence of these interactions will be corroborated by radioligand binding studies on synaptosomes derived from these terminals. In Specific Aim IV, studies on isolated ganglia devoid of axonal projections to muscle will characterize the interplay of modulatory interneurons and demonstrate the role of somatostatin interneurons as the neuronal switch between the two phases of the reflex. The combined approach embodied by these aims should advance our understanding of a major neuromuscular function.

该提议的目的是确定直接测量 肠感官，调节性和运动神经递质调节植物 肌肉拉伸和粘膜刺激引起蠕动反射 大鼠结肠和人类肠道。 我们以前的研究和初步 实验使我们确定了由 调节神经元与互惠的运动神经元结合 上升期间的循环和纵向肌肉活动 反射的下降阶段。 实验方法利用了小说 能够确定各个组成部分的准备工作 电路：（i）扁平地面隔室的肠段 特别测量感觉发射器的释放； （ii）纵向 肌肉条带有粘附的肌丛，可以识别 调节神经元与运动神经元的耦合支配纵向 肌肉; （iii）圆形的肌肉st裂，没有肌丛 测量发射机释放的突触前调节，从中到达 准备突触体以表征发射机与 突触前受体； （iv）新鲜分散的myenteric神经节 该检查调节调节中间神经元的反馈调节 丛。 在特定的目标I中，对大鼠结肠和人肠段的研究 将确定（a）组成的集成调节电路的作用 调节运动神经元的生长抑素，Enkephalin和GABA神经元 在上升期间支配循环和纵向肌肉 反射的下降阶段，以及（b）5-HT作用通过 神经元5-HT4受体在调节感觉发射器的释放时， CGRP和旋转金，物质P（SP）和Neurokinin A（NKA）。 在 特定的目标II，在肌丛l-dodududinal肌肉条中的研究 将证明调节电路通过VIP/PACAP/NOS神经元起作用 调节神经支配的胆碱能/速气蛋白运动神经元 纵向肌肉。 在特定的目标III中，对圆形肌肉的研究 仅包含轴突末端的条将确定 调节性之间的调节前（即轴 - 轴）相互作用 神经末端以及兴奋性和抑制性运动神经末端。 这 这些相互作用的存在将通过放射性结合来证实 从这些终端得出的突触体的研究。 在特定的目标IV中， 关于没有轴突投射到肌肉的孤立神经节的研究将 表征调节中间神经元的相互作用，并证明 生长抑素中间神经元的作用是两者之间的神经元切换 反射的阶段。 这些目标所体现的组合方法应该 促进我们对主要神经肌肉功能的理解。