PURINERGIC SIGNALING IN CULTURED HEART CELLS

培养心脏细胞中的嘌呤能信号传导

• 批准号: 6183116
• 负责人: BRUCE T LIANG
• 金额: $ 28.25万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183116
• 关键词: adenosine; adenosine triphosphate; adenylate cyclase; cardiac myocytes; chick embryo; cyclic AMP; cytoprotection; embryo /fetus tissue /cell culture; heart contraction; heart pharmacology; heart ventricle; isoproterenol; purinergic receptor; receptor coupling; receptor expression; receptor sensitivity; transfection

DESCRIPTION (Investigator's Abstract): Activation of adenosine receptors exerts important effects in the heart. The presence of a functional adenosine A3 receptor on the heart cell suggests a novel cardiac function for this receptor. Using cultured cardiac atrial and ventricular cells as models, the overall objective of the present proposal is to investigate the signaling mechanism, regulation, and function of the adenosine A3 receptor and to investigate the role of A1 and A3 receptors and the underlying mechanisms in preconditioning of cardiac myocytes. Specifically, the proposal will 1) carry out pharmacological characterization of the cardiac A3 receptor, 2) investigate the potential effectors, such as phospholipases, adenylyl cyclase and KATP channel, to which the A3 receptor is coupled, and 3) characterize desensitization of A3 receptor-coupled effectors. Because A1 and A3 receptors may have different signaling mechanisms and functions and may exhibit differential desensitization by adenosine agonist, parallel studies on the A1 receptor will be performed for direct comparison. Using a novel cardiac ventricular myocyte model of preconditioning, the proposal will further 4) investigate the role of A1 and A3 receptors in initiating and mediating the protective effect of preconditioning, and 5) study the mechanism by which activation of each receptor induces preconditioning and determine the role of protein kinase C and KATP channel in mediating this protective phenomenon. Moreover, atrial myocytes express only the A1 receptor and exhibit characteristics of preconditioning similar to the characteristics of A1 receptor-mediated preconditioning in the ventricular myocytes. Thus, atrial myocytes represent a useful "null" myocyte model for the A3 receptor and atrial myocytes transfected with A3 receptor cDNA will be used to further test the function and signaling mechanism of A3 receptor during preconditioning. The proposal should yield important and new information on the cardiac actions and signaling mechanisms of adenosine and its receptor subtypes.

描述（研究者的摘要）：腺苷受体的激活 在心脏中发挥重要影响。 功能的存在 心脏细胞上的腺苷A3受体提出了一种新颖的心脏功能 对于这个受体。 使用培养的心房和心室细胞作为 模型，本提案的总体目的是研究 腺苷A3受体的信号传导机制，调节和功能 并研究A1和A3受体的作用以及基础 心肌细胞预处理的机制。 具体来说， 建议将1）进行心脏的药理表征 A3受体，2）研究潜在效应子，例如磷脂酶， A3受体耦合的腺苷酸环化酶和KATP通道，并 3）表征A3受体偶联效应子的脱敏。 因为 A1和A3受体可能具有不同的信号传导机制和功能 并可能表现出腺苷激动剂的差异脱敏 对A1受体的研究将进行直接比较。 使用 新型心室心肌细胞模型，该建议 将进一步4）研究A1和A3受体在启动中的作用 并介导预处理的保护作用，5）研究 每个受体激活诱导预处理的机制和 确定蛋白激酶C和KATP通道在介导的作用 保护现象。 而且，心肌细胞仅表示A1 受体和展示特征的预处理类似 心室中A1受体介导的预处理的特征 心肌细胞。 因此，心房肌细胞代表了有用的“无效”肌细胞模型 用A3受体cDNA转染的A3受体和心肌细胞将 用于进一步测试A3受体的功能和信号传导机制 在预处理期间。 该提议应产生重要的新事物 有关腺苷的心脏作用和信号传导机制的信息 它的受体亚型。