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 是一种源自肾素-血管素原的八肽 该系统会引起与监管相关的广泛影响 血压以及盐和水的代谢。 确实，最 人类高血压的有效治疗剂通过阻断 血管紧张素II的形成。 广泛、长期的目标 拟议的研究是血管紧张素 II 的分子表征 受体。 该应用程序的具体目标是研究 分子上显然是血管紧张素 II 1 型受体的新形式 从大鼠垂体前叶克隆而来。 这个克隆不同于 最近描述的血管紧张素 II 1 型受体 平滑肌和肾脏。 受体的垂体形式具有 与血管/肾脏在核苷酸水平上总体一致性为 74% 受体；然而，它编码的蛋白质具有 95% 的氨基酸同一性。 两种形式受体的差异并不一致 选择性 RNA 剪接表明垂体和血管/肾 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 表达略有不同，垂体和血管 平滑肌显示出最高水平的同源受体。 最后，垂体的 mRNA 水平受到雌激素的强烈调节。 该提案的具体目标是：1）比较配体结合 两种形式受体的特征； 2）确定第二个 受体的垂体形式利用的信使系统； 3） 确定编码两者的 mRNA 的差异组织分布 受体的形式； 4）测试雌激素对mRNA表达的影响 不同组织中两种形式的受体； 5) 克隆、序列和 表征编码垂体形式受体的基因； 6） 分离、测序并表征人类垂体形态 受体； 7) 确定两种形式受体的细胞定位 使用原位杂交的mRNA，以及； 8) 产生单克隆抗体 衍生自两种形式的受体的肽。 这些研究 应提供有关人类病因和治疗的新信息 高血压。