ADENOSINE A1 AND A2 RECEPTORS IN THE MYOCARDIUM

心肌中的腺苷 A1 和 A2 受体

• 批准号: 6225862
• 负责人: JAMES G DOBSON
• 金额: $ 34.95万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-05 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6225862
• 关键词: G protein; adenosine; beta adrenergic receptor; cardiac myocytes; guanosinetriphosphatases; heart function; laboratory rat; muscarinic receptor; myocardium; protein kinase A; protein kinase C; protein protein interaction; purinergic receptor; receptor coupling; receptor sensitivity

DESCRIPTION (Verbatim from the application): Adenosine receptors play an important role in regulating cardiac function. For example, adenosine Al receptors affect heart rhythm, contraction and metabolism and mediate ischemic preconditioning. Adenosine by interacting with adenosine Al receptors is known to be antiadrenergic in that it reduces the contractile and metabolic responsiveness of the myocardium to beta1-adrenergic stimulation. Stimulation of adenosine A2a receptors has been reported to directly increase cardiac contractility. Recently we reported that adenosine A2a receptor stimulation also limits the antiadrenergic actions of adenosine. The mechanism by which the cardiac adenosine A2a receptors affect adenosine Al receptor function is not known. Furthermore, it is not known if A2a receptor actions also effect functioning of other receptors such as muscarinic receptor functioning. The objective of this project is to investigate the molecular mechanisms by which the adenosine A2a receptor inhibits adenosine Al receptor mediated antiadrenergic actions in the heart. Using rat ventricular myocytes and myocyte membranes, the proposed studies should reveal: 1) The way in which adenosine A2a receptor activation inhibits the antiadrenergic actions resulting from adenosine Al and muscarine M2 receptor stimulation, 2) The effect of adenosine A2a receptor action on f3 1-adrenergic, and adenosine Al ligand binding and beta1-adrenergic receptor sensitive adenylyl cyclase activity, 3) The importance of protein kinases A and C, G protein kinases, and receptor phosphorylation in the adenosine A2a receptor-mediated inhibition of adenosine Al-elicited antiadrenergic actions, and 4) The action of adenosine A2a receptor activation on adenosine Al receptor-mediated changes in GTPase activity upon beta1-adrenergic receptor stimulation. The results obtained from these studies should provide new information regarding the molecular functioning of adenosine receptors in the myocardium. Additionally, the findings should significantly contribute to our basic knowledge of the molecular mechanisms of G protein coupled receptor cross-regulation in the heart.

描述（逐字化的应用程序）：腺苷受体播放 在调节心脏功能中的重要作用。例如，腺苷Al 受体影响心律，收缩和代谢，并介导缺血性 预处理。腺苷与腺苷Al受体相互作用是已知的 要抗氧化能力，因为它可以减少收缩和代谢 心肌对β1-肾上腺素能刺激的反应。刺激 据报道，腺苷A2A受体直接增加心脏 收缩力。最近我们报道了腺苷A2A受体刺激 还限制了腺苷的抗氧化作用。该机制 心脏腺苷A2a受体影响腺苷Al受体功能不是 已知。此外，尚不清楚A2A受体作用是否也会影响 其他受体的功能，例如毒蕈碱受体功能。这 该项目的目的是研究分子机制 腺苷A2A受体抑制腺苷Al受体介导的 心脏中的抗氧化能力。使用大鼠心室肌细胞和心肌细胞 膜，拟议的研究应揭示：1）腺苷的方式 A2A受体激活抑制了由 腺苷Al和毒氨酸M2受体刺激，2）腺苷的作用 A2A受体对F3 1-肾上腺素和腺苷Al配体结合的作用和 beta1-肾上腺素受体敏感的腺苷酸环化酶活性，3） 蛋白激酶A和C，G蛋白激酶和受体的重要性 腺苷A2A受体介导的腺苷抑制作用中的磷酸化 AL引起的抗二氧化碳作用，4）腺苷A2A受体的作用 腺苷Al受体介导的GTPase活性变化的激活 β1-肾上腺素受体刺激。从这些研究中获得的结果 应该提供有关腺苷分子功能的新信息 心肌中的受体。此外，调查结果应明显 有助于我们对G蛋白分子机制的基本知识 心脏中耦合受体交叉调节。