Characterization of Cardiac Adenosine Receptor Systems

心脏腺苷受体系统的表征

• 批准号: 8719594
• 负责人: Richard Green
• 金额: $ 17.88万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-15 至 1992-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8719594&HistoricalAwards=false
• 关键词: Characterization; Cardiac; Adenosine; Receptor; Systems

Cardiac function is controlled by neurotransmitters, neuromodulators, and drugs that bind to specific receptors located on the cardiac membrane. These receptors interact with various effector mechanisms to regulate cellular activity. Adenosine is locally released in the heart and acts on specific extracellular, membrane.bound receptors to cause decrease in the rate and force of contraction of the heart. Furthermore, the rate of adenosine release in the myocardium is increased during exercise, hypoxia/ischemia and in the failing heart. However, little is known concerning the pharmacological and biochemical characteristics of adenosine receptors and adenosine receptor: effector mechanisms in cardiac cells. The long term goal of this project is to elucidate the mechanisms by which activation of adenosine receptors lead to the regulation of cardiac function so that pharmacological interventions affecting this system can ultimately be used to modify cardiac function. There are two specific aims: (1) Extensive pharmacological and biochemical experiments will be performed to further characterize the adenosine receptor(s) in the heart. These experiments will utilize three approaches: (a) ligand binding studies with both agonist and antagonist radioligands; (b) photoaffinity labelling; and (c) affinity chromatography and receptor purification. These experiments will determine if more than one type of adenosine receptor exists in the heart and whether the cardiac adenosine receptors are the same or different from adenosine receptors in the CNS. (2) Additional experiments will determine which effector system(s) is/are activated by cardiac adenosine receptors to result in the physiological changes induced by activation of adenosine receptors. The mechanisms by which cardiac receptors modulate cAMP levels in the heart will be probed and the possibility that adenosine receptors couple to other effector systems will be examined. The results are anticipated to provide fundamental insights to the processes by which adenosine receptors control cardiac function.

心脏功能是由神经递质、神经调节剂和药物控制的，这些药物与位于心膜上的特定受体结合。这些受体与各种效应机制相互作用以调节细胞活动。腺苷在心脏局部释放，作用于特定的细胞外膜。结合受体导致心脏收缩速率和收缩力的降低。此外，在运动、缺氧/缺血和心力衰竭时，心肌中腺苷的释放率增加。然而，关于腺苷受体的药理和生化特性以及腺苷受体在心脏细胞中的效应机制，我们知之甚少。该项目的长期目标是阐明腺苷受体激活导致心功能调节的机制，以便影响该系统的药物干预最终可用于改变心功能。有两个具体目的：(1)将进行广泛的药理学和生化实验，以进一步表征心脏中的腺苷受体。这些实验将采用三种方法：(a)与激动剂和拮抗剂放射配体的配体结合研究；(b)光亲和标记；(c)亲和层析和受体纯化。这些实验将确定心脏中是否存在不止一种腺苷受体，以及心脏腺苷受体与中枢神经系统中的腺苷受体是否相同或不同。(2)进一步的实验将确定哪些效应系统被心脏腺苷受体激活，从而导致由腺苷受体激活引起的生理变化。心脏受体调节心脏cAMP水平的机制将被探讨，腺苷受体与其他效应系统偶联的可能性将被研究。这些结果有望为腺苷受体控制心脏功能的过程提供基本的见解。