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RECEPTOR PHARMACY AND PHYSIOLOGY OF GUT PEPTIDES

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:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-09-01 至 1992-06-30

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中文摘要
翻译
这个应用程序的目的是确定分布、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 生理功能及管腔内含物的影响 外源性神经支配对受体分布和特性的影响。 速激肽受体将使用几种技术进行详细检查: A)定量放射自显影以确定分布和密度 胃肠道不同区域的受体 正常状态和后续操作研究;b)乳化液 放射自显影,由于其更高的分辨率,将允许 特定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,以允许 受体是否位于肌肉上的生化测定 突触体膜。解释这种区别是很重要的 文献中的矛盾之处。腔内含物对血管内皮细胞生长的影响 速激肽受体的分布和密度将使用 肠转流模型。外在神经支配的影响将是 使用肠道搭桥模型进行检查。外在的影响 神经支配将通过慢性迷走神经切断术和慢性迷走神经切断术进行检查 交感神经切除模型。在每一种情况下,放射自显影的结果都将是 与功能研究相关,如通过体外肌浴进行评估 大鼠和猫的制备及肌电的体内研究 以及肌电和收缩反应的收缩反应 大鼠远端回肠、回盲括约肌和结肠模型的实验研究 CAT,表现为颈内动脉对远端扩张的收缩反射和 颈内动脉对近端扩张的抑制反射。P物质有 已被证明可以调节收缩反应。关于中国传统文化的几点思考 多肽分布、受体分布与蛋白质合成的关系 生理效应将使我们能够确定 受体特性在控制肠道运动功能中的作用。这样的一个 测定在肠道运动疾病研究中的意义 在人类中,其中大部分没有解剖异常被描述。它 将表明对受体功能的研究是否可以提供洞察 这些定义不明确的疾病的病理生理学,导致 在美国发病率很高。
英文摘要
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.
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