MOLECULAR CHARACTERIZATION OF ANGIOTENSIN II RECEPTORS

血管紧张素 II 受体的分子表征

• 批准号: 3247025
• 负责人: JIMMY D NEILL
• 金额: $ 17.45万
• 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: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3247025
• 关键词: angiotensin II; estrogens; in situ hybridization; laboratory rat; molecular cloning; monoclonal antibody; neuropeptide receptor; pituitary gland; protein sequence; protein structure function; radiotracer; receptor binding; receptor expression; second messengers

Angiotensin II is an octapeptide derived from the renin-angiotinsenogen system which evokes a broad spectrum of effects related to regulation of blood pressure and to salt and water metabolism. Indeed, the most effective therapeutic agent for human hypertension acts by blocking the formation of angiotensin II. The broad, long-term objective of the proposed studies is the molecular characterization of angiotensin II receptors. The specific objective of this application is the study of an apparently new form of the angiotensin II, type 1 receptor molecularly cloned from the rat anterior pituitary gland. This clone differs from the angiotensin II, type 1 receptor recently described for vascular smooth muscle and kidney. The pituitary form of the receptor has an overall 74% identity at the nucleotide level with the vascular/kidney receptor; however, it encodes a protein with a 95% amino acid identity. The differences in the two forms of receptors are not consistent with alternative RNA splicing suggesting that the pituitary and vascular/renal receptors are encoded by separate genes. The ligand binding characteristics of the two forms of receptors are similar. Their tissue mRNA expression differs somewhat in that the pituitary and vascular smooth muscle show the highest levels of their cognate receptors. Finally, pituitary levels of mRNA are strongly regulated by estrogens. The Specific Aims of the proposal are to: 1) compare the ligand-binding characteristics of the two forms of receptors; 2) identify the second messenger system utilized by the pituitary form of the receptor; 3) determine the differential tissue distribution of mRNAs encoding the two forms of receptors; 4) test the effects of estrogens on mRNA expression of the two forms of receptors in various tissues; 5) clone, sequence, and characterize the gene encoding the pituitary form of the receptor; 6) isolate, sequence, and characterize the human form of the pituitary receptor; 7) determine the cell localization of the two forms of receptor mRNA using in situ hybridization, and; 8) produce monoclonal antibodies to peptides derived from the two forms of receptors. These studies should provide new information about the etiology and treatment of human hypertension.

血管紧张素II是源自肾素 - 血管紧宁原的八肽 引起与调节有关的广泛影响的系统 血压和盐和水代谢。 确实，最多 通过阻止人类高血压的有效治疗剂 血管紧张素II的形成。 广泛的长期目标 提出的研究是血管紧张素II的分子表征 受体。 该应用的具体目的是研究 显然是血管紧张素II的新形式，1型受体分子 从大鼠前垂体腺克隆。 这个克隆与 血管紧张素II，最近描述的1型受体 平滑肌和肾脏。 受体的垂体形式具有 血管/肾脏的核苷酸水平的总体身份总数为74％ 受体；但是，它编码具有95％氨基酸身份的蛋白质。 两种形式的受体的差异与 替代RNA剪接表明垂体和血管/肾脏 受体由单独的基因编码。 配体结合 两种形式的受体的特征相似。 他们的组织 mRNA表达有些不同，因为垂体和血管 平滑肌显示其同源受体的最高水平。 最后，mRNA的垂体水平受雌激素强烈调节。 该提案的具体目的是：1）比较配体结合 两种形式的受体的特征； 2）确定第二个 通过受体的垂体形式使用的使者系统； 3） 确定编码两者的mRNA的差分组织分布 受体的形式； 4）测试雌激素对mRNA表达的影响 在各种组织中的两种形式的受体中； 5）克隆，序列和 表征编码受体垂体形式的基因； 6） 分离，序列和表征垂体的人类形式 受体； 7）确定两种形式的受体的细胞定位 mRNA使用原位杂交，并且； 8）产生单克隆抗体 从两种形式的受体衍生的肽。 这些研究 应该提供有关人类病因和治疗的新信息 高血压。