Characterization of Cardiac Adenosine Receptor Systems

心脏功能由神经递质控制， 神经调节剂和与特定受体结合的药物 位于心脏膜上。 这些受体与 调节细胞活性的各种效应器机制。 腺苷在心脏局部释放，作用于特定的 细胞外，膜。结合受体，导致减少， 心脏收缩的速度和力量。 而且 心肌中腺苷释放的速率增加， 运动、缺氧/缺血和心脏衰竭。 然而，在这方面， 关于其药理学和生物化学性质知之甚少。 腺苷受体和腺苷受体的特征： 心脏细胞中的效应器机制。 长期目标是 该项目旨在阐明激活 腺苷受体调节心脏功能， 影响这个系统的药物干预可以 最终用于改善心脏功能。 有两 具体目的：（1）广泛的药理学和生物化学 将进行实验以进一步表征 心脏中的腺苷受体。 这些实验将 利用三种方法：（a）配体结合研究， 激动剂和拮抗剂放射性配体;（B）光亲和标记; 和（c）亲和层析和受体纯化。 这些 实验将确定是否有一种以上的腺苷 受体存在于心脏中，心脏腺苷是否 受体与腺苷受体相同或不同， CNS。 (2)更多的实验将确定 效应系统被心脏腺苷激活 受体，导致生理变化引起的 腺苷受体的激活。 的机制 心脏受体调节心脏中的cAMP水平， 研究了腺苷受体与 将检查其它效应器系统。 结果 预计将提供基本的见解的进程， 腺苷受体控制心脏功能。

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.