Novel aspects of angiotensin AT1 receptor signalling pathways

激素是一种释放到血液中的化学物质，通过与特定组织中细胞上的特定部位（受体）结合来影响组织功能。一般来说，人们认为特定的受体在与激素结合时激活特定的反应。然而，现在很清楚的是，即使它们与一种受体结合，密切相关的激素也能激活不同的反应模式。这一现象的全部后果尚不清楚。本项目将研究其对参与血压控制的重要激素的意义。肾素-血管紧张素系统产生激素血管紧张素II，通过心脏、血管、神经和肾脏的作用使血压升高。一种特殊的受体类型，AT1受体，负责血管紧张素II对这些组织的大部分影响，抑制这种受体活性的药物对高血压和心力衰竭等疾病非常有用。然而，血管紧张素III是肾素-血管紧张素系统的第二种激素，当它激活AT1受体时，也可能对组织功能产生重要影响。我们有证据表明，由血管紧张素III激活的AT1受体引起的组织反应类型与由血管紧张素II激活相同受体引起的组织反应类型不同。这提出了AT1受体在心血管疾病中的作用可能是由两种血管紧张素不同地促进的可能性。该项目将研究血管紧张素II和血管紧张素III通过AT1受体引起不同激活的机制，并将确定这种差异激活对组织功能的影响。

Hormones are chemicals released into the blood to influence tissue function by binding to specific sites (receptors) located on the cells found in a particular tissue. In general, it has been considered that a specific receptor activates a specific response when bound by the hormone. However, it is now clear that closely related hormones can activate different patterns of response even when they bind the one type of receptor. The full consequence of this phenomenon is still unknown. Its significance will be investigated in this project for important hormones which are involved in blood pressure control. The renin-angiotensin system makes the hormone angiotensin II which increases blood pressure through actions the heart, blood vessels, nerves and kidneys. One particular receptor type, the AT1 receptor, is responsible for the majority of effects of angiotensin II on these tissues and drugs that inhibit the activity of this receptor are very useful therapies for diseases such as hypertension and heart failure. However, Angiotensin III is a second hormone of the renin-angiotensin system that may also have important effects on tissue function when it activates the AT1 receptor. We have evidence that the type of tissue response that results from angiotensin III activated AT1 receptors is different from the response that results from angiotensin II activation of the same receptors. This raises the possibility that the effects of the AT1 receptor in cardiovascular disease might be differentially promoted by the two angiotensins. This project will investigate the mechanisms by which angiotensin II and anagiotensin III can elicit different activation via the AT1 receptor, and will determine the consequences of this differntial activation to tissue function.