CHARACTERIZATION OF CARDIAC ADENOSINE RECEPTORS

心脏腺苷受体的特征

• 批准号: 3357846
• 负责人: RICHARD D GREEN
• 金额: $ 16.49万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3357846
• 关键词: adenosine; adenylate cyclase; affinity chromatography; atrium; chickens; exercise; extracellular matrix; heart cell; heart contraction; heart failure; heart function; heart ventricle; hormone receptor; hormone regulation /control mechanism; laboratory rabbit; myocardial ischemia /hypoxia; neurotransmitter receptor; neurotransmitters; potassium channel

Cardiac function is controlled by neurotransmitters, neuromodulators, and drugs which bind to specific receptors located on the cardiac membrane. These receptors interact with various effector systems to regulate cellular activity. It is now recognized that adenosine is locally released in the heart and that it acts on specific extracellular, membrane bound receptors to cause decreases in the rate and force of contraction of the heart. Furthermore, it is known that the rate of adenosine release in the myocardium is increased during exercise, hypoxia/ischemia and in the failing heart. While we know that cardiac adenose receptors (AdoRs) couple to K channels in the atria and to adenylate cyclase in both the ventricle and the atria, we know little about the cardiac AdoR itself. This is largely due to the relative paucity of AdoRs in cardiac tissue. The long term goal of this project is to isolate and characterize cardiac AdoRs. Cardiac AdoRs have characteristics similar to the A(1) AdoR which is present in the brain. As the concentration of these receptors is much higher in the brain compared to the heart, our initial goal is to purify the brain A(1) AdoR. We will do this using a combination of affinity chromatography and classical protein purification techniques; polyclonal antibodies against this AdoR and peptide fragments thereof will subsequently be prepared. A combination of affinity chromatography, protein purification techniques and immunoaffinity chromatography will be used to isolate cardiac AdoRs. Affinity labeling and peptide mapping experiments will be performed to compare the properties of the cardiac and neural AdoR to determine if subtypes of AdoRs exist. Furthermore, we will compare the properties of A(1) AdoRs in atria and ventricle in order to begin to probe the possibility that different types of A(1) receptors couple to different effectors, e.g., K Channels and adenylate cyclase.

心脏功能由神经递质、神经调节剂和 与位于心脏膜上的特定受体结合的药物。 这些受体与各种效应系统相互作用以调节细胞 活动。现在人们认识到腺苷是在体内局部释放的。 心脏并作用于特定的细胞外膜结合受体 导致心脏收缩速度和力量下降。 此外，众所周知，腺苷释放速率 运动、缺氧/缺血和 失败的心。虽然我们知道心脏腺糖受体（AdoRs）耦合 心房中的 K 通道和心室中的腺苷酸环化酶 和心房，我们对心脏 AdoR 本身知之甚少。这是 主要是由于心脏组织中 AdoR 相对较少。长的 该项目的长期目标是分离和表征心脏 AdoR。 心脏 AdoR 具有与 A(1) AdoR 类似的特征，即 存在于大脑中。由于这些受体的浓度非常高 与心脏相比，大脑的位置更高，我们最初的目标是净化 大脑 A(1) AdoR。我们将使用亲和力的组合来做到这一点 色谱法和经典的蛋白质纯化技术；多克隆 针对该 AdoR 的抗体及其肽片段将 随后做好准备。亲和层析、蛋白质的组合 纯化技术和免疫亲和层析将用于 分离心脏 AdoR。亲和标记和肽图谱实验 将进行比较心脏和神经 AdoR 的特性 以确定 AdoR 的亚型是否存在。此外，我们将比较 A(1) AdoRs 在心房和心室中的特性，以便开始探测 不同类型的 A(1) 受体与不同类型的 A(1) 受体偶联的可能性 效应子，例如 K 通道和腺苷酸环化酶。