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CHARACTERIZATION OF CARDIAC ADENOSINE RECEPTORS

心脏腺苷受体的特征

基本信息

批准号：
2219660
负责人：
RICHARD D GREEN
金额：
$ 15.17万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-07-01 至 1995-06-30
项目状态：
已结题

项目摘要

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肌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，调节细胞活动。现在已经认识到，腺苷在体内局部释放。它作用于特定的细胞外、膜结合的受体使心脏收缩的速度和力量减慢。此外，已知的是腺苷在体内的释放速率在运动、缺氧/缺血期间和在心脏衰竭。虽然我们知道心肌腺糖受体(ADOR)对心房的K通道和两个心室的腺化环化酶至于心房，我们对心脏多发本身知之甚少。这是这在很大程度上是由于心脏组织中ADO受体的相对缺乏所致。《长河》本项目的长期目标是分离和鉴定心脏ADORs。心脏ADOR具有类似于A(1)ADR的特征存在于大脑中。因为这些受体的浓度很高与心脏相比，大脑的含量更高，我们最初的目标是净化大脑A(1)多德。我们将使用亲和力的组合来实现这一点层析和经典蛋白质纯化技术；多克隆针对该多克隆抗体及其多肽片段将随后要做好准备。结合亲和层析、蛋白质纯化技术和免疫亲和层析将用于分离心脏ADORs。亲和标记和多肽图谱实验以比较心脏和神经血管的特性以确定是否存在ADOR的子类型。此外，我们将比较 A(1)ADORs在房室内的特性以便开始探测不同类型的A(1)受体与不同受体结合的可能性效应器，如K通道和腺苷环化酶。