ANGIOTENSIN II RECEPTOR GENE EXPRESSION

血管紧张素 II 受体基因表达

• 批准号: 3473958
• 负责人: TERRY S ELTON
• 金额: $ 9.7万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473958
• 关键词: G protein; angiotensin /renin /aldosterone hypertension; angiotensin II; disease /disorder model; gene expression; hormone receptor; laboratory rat; molecular genetics; molecular pathology; northern blottings; polymerase chain reaction; restriction mapping; spontaneous hypertensive rat; transfection

Angiotensin II (AII), the biologically active component of the renin- angiotensin system, has a variety of physiological effects in many tissues. In addition, AII is an important pathogenic factor in some forms of clinical and experimental hypertension. Currently, the cellular and molecular mechanism(s) of action of AII are not well understood. AII interacts with two pharmacologically distinct subtypes of cell-surface receptors, AT1 and AT2. AT1 receptors couple to specific G-proteins and mediate most, if not all, of the well known effects of AII. Recently several cDNA clones encoding the AII receptor subtype, AT1, have been isolated and characterized. An AT1 receptor PCR amplified fragment was utilized by our laboratory as a radiolabeled probe to isolate several distinct rat genomic AT1 receptor clones. Preliminary data suggest that there are at least two AII receptor genes. The long term goal of this project is to define the AII receptor gene family and to examine the molecular mechanisms that regulate the expression of these receptors. The Specific Aims are: 1) Characterize, compare and contrast the two distinct rat genomic AII receptor clones by restriction mapping and sequencing. The genes will be expressed and their activities compared. A comparison of tissue specific expression of these genes will also be carried out; 2) The role of AII in the modulation of AII receptor gene expression will be investigated by quantitating and comparing steady state mRNA levels of AII receptors in vascular smooth muscle cells isolated from normotensive and spontaneously hypertensive rats and in tissues from intact rats of these strains infused with exogenous AII or treated with deoxycorticosterone (DOCA) salt. 3) The cis-regulatory mechanism involved in selectively directing the transcription of the AII receptor promoters will be investigated utilizing DNA-mediated gene transfer. These studies will contribute to our basic understanding of the molecular mechanisms underlying AII gene expression in normal animals and will investigate whether AII gene expression is altered in a genetic hypertensive model.

血管紧张素II（AII），肾素的生物活性成分， 血管紧张素系统在许多组织中具有多种生理作用。 此外，AII在某些形式的 临床和实验性高血压。 目前，蜂窝和 AII作用的分子机制尚不清楚。 AII 与两种截然不同的细胞表面亚型相互作用 受体，AT1和AT2。 AT1受体与特定的G蛋白偶联， 介导了AII的大多数（如果不是全部的话）众所周知的效应。 最近 已经克隆了几个编码AII受体亚型AT1的cDNA克隆， 分离并表征。 用PCR方法扩增AT1受体片段， 我们的实验室利用放射性标记探针分离出几种 不同的大鼠基因组AT1受体克隆。 初步数据显示， 存在至少两个AII受体基因。 长期目标是 项目是定义AII受体基因家族， 调节这些受体表达的分子机制。 具体目的是：1）对两者进行定性、比较和对比 不同的大鼠基因组AII受体克隆， 测序 将表达基因并比较它们的活性。 一 还将比较这些基因的组织特异性表达， AII在AII受体基因调控中的作用 将通过定量和比较稳态来研究表达 血管平滑肌细胞AII受体的mRNA水平 正常血压和自发性高血压大鼠和来自完整组织的组织中 这些品系的大鼠输注外源性AII或用 脱氧皮质酮（DOCA）盐。 3)顺式调节机制涉及 在选择性地指导AII受体启动子的转录中， 将利用DNA介导的基因转移进行研究。 这些研究 将有助于我们对分子机制的基本理解 在正常动物中潜在的AII基因表达，并将研究 在遗传性高血压模型中AII基因表达是否改变。