RECEPTOR PHARMACY AND PHYSIOLOGY OF GUT PEPTIDES

肠肽的受体药学和生理学

• 批准号: 3232493
• 负责人: Ann Ouyang
• 金额: $ 8.49万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232493
• 关键词: autoradiography; biological models; cats; colon; drug receptors; gastrointestinal motility /pressure; ileum; innervation; laboratory rat; neuropeptide receptor; physiology; radiotracer; stomach /intestine bypass; substance P; sympathectomy; synaptosomes; vagotomy

The aim of this application is to determine the distribution, density and properties of tachykinin receptors in the intestine of the rat and cat and to determine the relationship between receptor properties and physiologic function and to examine the effect of intraluminal contents and extrinsic innervation on the receptor distribution and properties. Tachykinin receptors will be examined in detail using several techniques: a) quantitative autoradiography to determine the distribution and density of receptors in different areas of the gastrointestinal tract both in the normal state and following manipulation studies; b) emulsion autoradiography which, as a result of its higher resolution, will allow correlation of specific binding with microscopic structures; and c) binding studies using purified membrane preparations to allow the biochemical determination of whether the receptors are located on muscle membrane of synaptasomes. This distinction is important to explain discrepancies in the literature. The effect of intraluminal contents on tachykinin receptor distribution and density will be examined using an intestinal bypass model. The effects of extrinsic innervation will be examined using an intestinal bypass model. The effects of extrinsic innervation will be examined by the use of chronic vagotomy and chronic sympathectomy models. In each case, autoradiographic findings will be correlated with functional studies, as assessed by in vitro muscle bath preparations in the rat and cat and in vivo studies of the myoelectrical and contractile responses of the myoelectrical and contractile responses of the distal ileum, ileocecal sphincter (ICS) and colon model in the cat; which shows a contractile reflex at the ICS to distal distension and an inhibitory reflex at the ICS to proximal distention. Substance P has been shown to mediate the contractile response. A study of the relationship between peptide distribution, receptor distribution and physiological effect will allow a determination of the significance of receptor properties in the control of intestinal motor function. Such a determination has implications in the study of intestinal motor diseases in man, in most of which no anatomic abnormality has been described. It will indicate whether studies of receptor function may provide insight into the pathophysiology of these poorly defined disorders, which result in significant morbidity in the United States.

本申请的目的是确定分布，密度和 大鼠和猫肠道速激肽受体的特性 并确定受体特性与 生理功能，并检查管腔内容物的作用 和外源性神经支配对受体分布和性质的影响。 将使用以下几种技术详细检查速激肽受体： a）定量放射自显影以确定分布和密度 在胃肠道的不同区域， 正常状态和后续操作研究; B）乳剂 放射自显影，由于其较高的分辨率， 特异性结合与微观结构的相关性;以及c） 使用纯化的膜制剂进行结合研究， 受体是否位于肌肉上的生物化学测定 突触体膜。 这个区别很重要， 文献中的差异。 管腔内容物对 速激肽受体的分布和密度将使用 肠旁路模型。 外部神经支配的影响将是 使用肠旁路模型检查。 外在的影响 神经支配将通过使用慢性迷走神经切断术和慢性迷走神经切断术来检查。 交感神经切除模型。 在每种情况下，放射自显影结果将 与功能研究相关，通过体外肌肉浴评估 在大鼠和猫中的制备和在体内研究的肌电 肌电和收缩反应的收缩反应 远端回肠，回盲部括约肌（ICS）和结肠模型， 猫;显示ICS处对远端扩张的收缩反射， ICS对近端扩张的抑制反射。 P物质具有 被证明可以调节收缩反应。 的研究 肽分布、受体分布和 生理效应将允许确定 在控制肠运动功能中的受体特性。 这样的 测定在肠运动疾病的研究中有意义 其中大多数没有解剖学异常。 它 将表明受体功能的研究是否可以提供洞察力 这些定义不清的疾病的病理生理学， 在美国的发病率很高。