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 是某些形式的重要致病因素。 临床和实验性高血压。 目前，蜂窝和 AII 的分子作用机制尚不清楚。 全部 与细胞表面两种药理学不同的亚型相互作用 受体 AT1 和 AT2。 AT1 受体与特定的 G 蛋白偶联 介导 AII 的大部分（如果不是全部）众所周知的影响。 最近 编码 AII 受体亚型 AT1 的几个 cDNA 克隆已被 分离并表征。 AT1受体PCR扩增片段是 我们的实验室使用放射性标记探针来分离几种 不同的大鼠基因组 AT1 受体克隆。 初步数据表明 至少有两个AII受体基因。 本次活动的长远目标 项目的目的是定义 AII 受体基因家族并检查 调节这些受体表达的分子机制。 具体目标是： 1) 描述、比较和对比两者 通过限制性图谱绘制不同的大鼠基因组 AII 受体克隆 测序。 基因将被表达并比较它们的活性。 一个 这些基因的组织特异性表达的比较也将 执行; 2）AII在AII受体基因调节中的作用 将通过定量和比较稳态来研究表达 血管平滑肌细胞中 AII 受体 mRNA 水平 正常血压和自发性高血压大鼠以及完整的组织 这些品系的大鼠被注入外源性 AII 或用 脱氧皮质酮（DOCA）盐。 3）涉及的顺式调节机制 选择性指导 AII 受体启动子的转录 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 正常动物中潜在的 AII 基因表达，并将进行研究 遗传性高血压模型中 AII 基因表达是否发生改变。