Arresting type 1 angiotensin receptors

抑制 1 型血管紧张素受体

• 批准号: nhmrc : 268925
• 负责人: Prof Alexander Smith
• 金额: $ 23.3万
• 依托单位: Baker IDI Heart and Diabetes Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/arresting-type-1-angiotensin-receptors/98415
• 关键词: Arresting; type; angiotensin; receptors

Our bodies generate a hormone called angiotensin II in response to a decrease in blood pressure (or salt in our bloodstream). This hormone increases blood pressure by causing blood vessels to constrict, by making us thirsty, and by inducing salt and fluid retention via an effect on the kidneys. In some cardiovascular diseases, the generation of angiotensin II or our sensitivity to this hormone is elevated. It is therefore crucial that we understand how angiotensin II works and how its actions in the body are mediated. For angiotensin II to act it must first bind to a receptor. Receptors are proteins and behave like locks that are opened by the hormone keys. Thus, cellular receptors for angiotensin II are engaged and activated by increases in angiotensin II in our blood. These receptors then produce signals which initiate a response (e.g. constriction of a blood vessel). Subsequently, the receptors are switched-off to prevent over-stimulation. The experiments proposed in this application continue our investigations into how angiotensin II receptors are regulated or switched-on and -off. A major way for receptors to be turned off is for them to be ear-marked by a modification known as phosphorylation. These modified receptors are then bound by proteins termed arrestins, which as indicated by their name play a role in preventing further receptor signalling. These arrestins also help remove activated receptors from the cell surface to the inside of the cell. How arrestins interact with receptors and regulate their function is poorly understood. This application proposes experiments to investigate the molecular mechanisms of arrestin action as it relates to the angiotensin II receptor. Results from these studies will further our understanding of angiotensin II receptors and their role in cardiovascular control.

我们的身体产生一种称为血管紧张素II的激素，以应对血压（或血液中的盐）的下降。这种激素通过引起血管收缩，使我们口渴，并通过对肾脏的影响诱导盐和液体潴留来增加血压。在某些心血管疾病中，血管紧张素II的生成或我们对这种激素的敏感性升高。因此，我们了解血管紧张素II如何工作以及它在体内的作用是如何介导的至关重要。血管紧张素II要发挥作用，必须首先与受体结合。受体是蛋白质，其行为就像是由激素钥匙打开的锁。因此，血管紧张素II的细胞受体通过我们血液中血管紧张素II的增加而参与和激活。然后这些受体产生信号，引发反应（例如血管收缩）。随后，受体被关闭以防止过度刺激。本申请中提出的实验继续我们对血管紧张素II受体如何被调节或打开和关闭的研究。受体被关闭的一个主要方式是通过一种被称为磷酸化的修饰使它们被标记。然后，这些修饰的受体被称为抑制蛋白的蛋白质结合，正如其名称所示，抑制蛋白在阻止进一步的受体信号传导中发挥作用。这些抑制蛋白还有助于将激活的受体从细胞表面转移到细胞内部。arrestins如何与受体相互作用并调节其功能还知之甚少。本申请提出了研究arrestin作用的分子机制的实验，因为它涉及血管紧张素II受体。这些研究的结果将进一步加深我们对血管紧张素II受体及其在心血管控制中的作用的理解。