V1-VASCULAR VASOPRESSIN RECEPTORS OF MESANGIAL CELL

V1-系膜细胞血管加压素受体

• 批准号: 6242032
• 负责人: MARC THIBONNIER
• 金额: $ 22.19万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6242032
• 关键词: G protein; affinity chromatography; angiotensin /renin /aldosterone hypertension; arginine vasopressin; biological signal transduction; calcium flux; gene expression; hormone receptor; hormone regulation /control mechanism; human tissue; ion transport; kidney cell; laboratory rat; molecular cloning; monoclonal antibody; platelets; protein kinase C; protein purification; protooncogene; receptor binding; renal glomerulus; spontaneous hypertensive rat; tissue /cell culture; vascular resistance; vasomotion

Vasopressin (AVP) is not only a potent antidiuretic and vasoconstrictor hormone but it also stimulates platelet aggregation, blood coagulation factors production, glucose release and fibroblast proliferation. All these actions may mediate the involvement of AVP in the development of arterial hypertension and atherosclerosis, the leading causes of human mortality. The long-term objectives of our research dedicated to AVP are: 1) to delineate the role played by AVP in the development of arterial hypertensin (HTA) and atherosclerosis, 2) to purify and clone AVP receptors in order to: a) design non peptide orally active AVP antagonists to be used in diseases characterized by AVP-induced alterations of blood volume, blood pressure, and blood coagulation, b) identify the molecular defect underlying the resistance to the peripheral actions of AVP in the nephrogenic type of diabetes insipidus. Using human and rat glomerular mesangial cells (GMC) in culture, the goals of the present proposal are to: 1) explore the complete cascade of events following binding of AVP to its specific membrane V1-vascular receptors and isolate any alteration explaining the increased vascular reactivity to AVP noted in genetically and DOCA-salt hypertensive rats. 2) purify the human and rat V1-vascular AVP receptors.

加压素（AVP）不仅是一种有效的抗利尿剂和血管收缩剂 激素，但还刺激血小板聚集，血液凝结 因素产生，葡萄糖释放和成纤维细胞增殖。 全部 这些行动可能调解AVP参与的发展 动脉高血压和动脉粥样硬化，人类的主要原因 死亡。 我们专门针对AVP的研究的长期目标是：1） 描述AVP在动脉发展中所扮演的角色 催眠蛋白（HTA）和动脉粥样硬化，2）净化和克隆AVP 受体以：a）设计非肽口服活性AVP 拮抗剂用于以AVP诱导为特征的疾病 血液体积，血压和血液凝结的改变，b） 识别抗性的分子缺陷 AVP在糖尿病肾脏类型的外围作用。 在培养中使用人和大鼠肾小球肾小球细胞（GMC） 本提案的目标是：1）探索完整的级联 AVP与其特定膜V1血管结合后的事件 受体并分离任何改变血管增加的改变 对AVP的反应性在遗传和DOCA盐高血压大鼠中指出。 2）净化人和大鼠V1血管AVP受体。