GASTROINTESTINAL CONTROL BY NEUROPEPTIDES

该应用程序代表了三个重要的系统详细的研究 参与消化系统调节的神经肽系统， 其他内脏器官。 调查将集中在阿片肽， 速激肽（P物质、K物质等）和胆囊收缩素 （CCK）。 重点贯穿于神经肽机制的理解 与其药理作用、生理作用 和生化特性。 核心假设是神经肽在感觉和感觉中起作用。 大脑、脊髓和外周的运动通路来调节 胃肠道的生理活动，膀胱， 血管和其他内脏器官。 具体监管事件 由单个神经肽启动或调节的反映神经递质 在多个解剖部位介导的多个受体亚型的作用 通过多种分子形式，并涉及与其他 管制物质。 因为神经肽的复杂性 行动和相互作用，需要一个全面的研究计划， 同时处理多个生物水平的机制， 采用多种实验方法。 即使有大量的合作 尽管如此，并不是所有的肽都可以同时研究。 我们将重点关注三个 特定的肽类（阿片类，速激肽和CCK）被认为是 参与内脏反射通路的感觉和运动成分。 选择阿片肽是因为已知它们可以产生强大的 对胃肠和膀胱运动的调节作用. 大脑，脊髓和肌壁内部位， 药理学工具可用于他们的研究（表1）。 速激肽 已知在感觉和运动通路中起作用， 多层次的阿片系统。 胆囊收缩素（CCK）在很大程度上 代表了与肠道相关的感觉和运动通路， 似乎以特定的方式与阿片系统相互作用。

This application represents a systematic detailed study of three important neuropeptide systems involved in regulation of the digestive system and other visceral organs. The investigations will focus on opioid peptides, tachykinins (substance P, substance K and others), and cholecystokinin (CCK). Emphasis throughout is on understanding of neuropeptide mechanisms of action relevant to their pharmacological effects, physiological roles, and biochemical characteristics. The central hypothesis is that neuropeptides function in both sensory and motor pathways in the brain, spinal cord and periphery to regulate physiological activity of the gastrointestinal tract, urinary bladder, blood vessels, and other visceral organs. The specific regulatory events initiated or modulated by individual neuropeptides reflect neurotransmitter actions at multiple receptor subtypes in multiple anatomical sites mediated by multiple molecular forms and involving multiple interactions with other regulatory substances. Because of the complexities of the neuropeptide actions and interactions, a comprehensive research program is required that simultaneously addresses mechanisms at multiple biological levels and employs multiple experimental approaches. Even with a large collaborative effort, not all peptides can be studied at once. We will focus on three specific peptide groups (opioids, tachykinins and CCK) thought to be involved in both sensory and motor components of visceral reflex pathways. Opioid peptides were chosen because they are known to exert powerful regulatory effects on gastrointestinal and bladder motility by actions at brain, spinal cord and intramural sites and because an array of pharmacological tools in available for their study (Table 1). Tachykinins are known to function in both sensory and motor pathways and to interact at multiple levels with opioid systems. Cholesystokinin (CCK) is heavily represented in sensory and motor pathways relevant to the gut and also appears to interact in specific ways with opioid systems.