Novel functional domains on adrenoceptors for drug interaction and cell signalling

肾上腺素受体上用于药物相互作用和细胞信号传导的新功能域

• 批准号: nhmrc : 236884
• 负责人: Dr Bronwyn Evans
• 金额: $ 53.44万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-functional-domains-cell-signalling/96192
• 关键词: Novel; functional; domains; adrenoceptors; drug

Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the major group of cell surface receptors that interact with hormones and neurotransmitters. Treatment of many diseases and conditions relies on the use of drugs that selectively activate or block a single type of GPCR. In fact, about 2-3 of existing therapies are based on these drugs. In designing new drugs it is important to understand as much as possible about the properties of the target receptors. There is emerging evidence concerning interactions between drugs, receptors and proteins inside cells that translate signals into responses (signalling proteins). For example, receptors have additional sites of drug action that can modulate their activity, and can also couple to multiple signalling pathways. We are studying adrenoceptors that respond to adrenaline and to the neurotransmitter noradrenaline. Our studies will use adrenoceptors as model systems to identify novel potential sites for drug interaction, to gain new insights into signalling mechanisms utilized by these receptors and to examine how a variety of phosphorylation mechanisms affect the ability of receptors to couple to particular signalling pathways.

我们的工作涉及研究细胞表面蛋白质（受体），这些蛋白质对肾上腺素等激素或神经系统中传递信号的物质（神经递质）做出反应。这些受体在协调对刺激的反应中起着至关重要的作用，这些刺激包括压力，疼痛，血压，体温，液体和能量状态以及运动的变化。它们允许不同器官或神经系统不同部分之间的通信。G蛋白偶联受体（GPCR）是与激素和神经递质相互作用的主要细胞表面受体。许多疾病和病症的治疗依赖于选择性激活或阻断单一类型GPCR的药物的使用。事实上，大约2-3种现有的治疗方法是基于这些药物。在设计新药时，尽可能多地了解靶受体的特性是很重要的。有新的证据表明，药物、受体和细胞内将信号转化为反应的蛋白质（信号蛋白）之间存在相互作用。例如，受体具有额外的药物作用位点，可以调节其活性，并且还可以与多种信号传导途径偶联。我们正在研究对肾上腺素和神经递质去甲肾上腺素有反应的肾上腺素受体。我们的研究将使用肾上腺素受体作为模型系统，以确定新的药物相互作用的潜在位点，获得新的见解，这些受体所利用的信号传导机制，并研究各种磷酸化机制如何影响受体的能力，耦合到特定的信号传导途径。