ANGIOTENSIN RECEPTOR AT1 IN VASCULAR CELL CONTROL

血管紧张素受体 AT1 在血管细胞控制中的作用

• 批准号: 2685533
• 负责人: TADASHI INAGAMI
• 金额: $ 34.86万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-10 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685533
• 关键词: angiotensin II; biological signal transduction; enzyme induction /repression; hormone receptor; immunologic assay /test; laboratory rabbit; laboratory rat; mitogen activated protein kinase; phospholipase C; protein structure function; receptor binding; receptor coupling; receptor sensitivity; tissue /cell culture; vascular smooth muscle; yeast two hybrid system

DESCRIPTION: (Adapted from the Applicant's Abstract) A large portion of the population is afflicted by the hypertensive and cardiovascular degenerative effects of AII. Because plasma levels of AII are often normal in the above disease states, abnormalities are likely to exist in receptor regulation and/or cell signaling, the mechanisms of which are complex and not fully understood. The applicant will use vascular smooth muscle cells in culture to i) define the C-terminal domain responsible for activation of phospholipase C; ii) investigate and identify the mechanisms of cross-talk by which the G-protein-coupled receptor activates MAPkinase via calcium calmodulin kinase; iii) identify receptor binding proteins responsible for receptor internalization and the mechanism of desensitization; and iv) down regulation of the AT1 mRNA by destabilization of the mRNA. The focus is on the dominant vasoconstrictor, mitogenic, hypertrophic receptor (AT1) and the regulatory function of the cytosolic C-terminal region. Techniques to be used include receptor antibodies, AT1 engineered mutant, the yeast two hybrid system, and specific new inhibitors and assay techniques. The approach using cellular and molecular tools will provide significant new information on complex receptor regulation and signaling and thus insights into potential defects in and therapy for various vascular diseases.

描述：（改编自申请人的摘要）大部分 人群受到高血压和心血管退化的困扰 AII 的影响。 因为AII的血浆水平在上述情况下通常是正常的 疾病状态下，受体调节可能存在异常 和/或细胞信号传导，其机制复杂且不完全 明白了。 申请人将在培养物中使用血管平滑肌细胞 i) 定义负责激活的 C 端域 磷脂酶C； ii) 研究并确定串扰机制 G 蛋白偶联受体通过钙激活 MAPkinase 钙调蛋白激酶； iii) 鉴定负责的受体结合蛋白 受体内化和脱敏机制； iv) 向下 通过 mRNA 的不稳定来调节 AT1 mRNA。 重点是 主要的血管收缩、促有丝分裂、肥大受体 (AT1) 和 细胞质C末端区域的调节功能。 技术要 使用的包括受体抗体、AT1工程突变体、酵母两种 混合系统，以及特定的新抑制剂和测定技术。 这 使用细胞和分子工具的方法将提供重要的新 有关复杂受体调节和信号传导的信息以及见解 研究各种血管疾病的潜在缺陷和治疗方法。