ADENOSINE A1 AND A2 RECEPTORS IN THE MYOCARDIUM

描述(来自应用程序的逐字)：腺苷受体在 在调节心脏功能方面发挥重要作用。例如，腺苷Al 受体影响心脏节律、收缩和代谢，并介导缺血 预适应。腺苷通过与腺苷Al受体相互作用是已知的 抗肾上腺素能，因为它减少了收缩和新陈代谢 心肌对β1-肾上腺素能刺激的反应性。刺激 已有报道称腺苷A2a受体可直接增加心脏 伸缩性。最近我们报道了腺苷A2a受体刺激 也限制了腺苷的抗肾上腺素能作用。这是一种机制 心脏腺苷A2a受体对腺苷A1受体功能的影响 为人所知。此外，目前还不知道A2a受体的作用是否也影响 其他受体的功能，如M受体的功能。这个 本项目的目标是研究通过这些分子机制 腺苷A2a受体抑制腺苷A1受体介导 心脏中的抗肾上腺素能作用。利用大鼠心肌细胞和肌细胞 膜，拟议的研究应该揭示：1)腺苷 A2A型受体的激活可抑制阿片受体的抗肾上腺素能作用 腺苷A1和M_2受体兴奋，2)腺苷的作用 A2a受体在f31-肾上腺素能上的作用，以及腺苷Al配体结合和 β1-肾上腺素能受体敏感的腺酰环化酶活性，3) 蛋白激酶A、C、G及其受体的重要性 腺苷A2a受体介导的腺苷抑制中的磷酸化 4)腺苷A2a受体的作用 激活腺苷Al受体介导的GTP酶活性变化 β1-肾上腺素能受体刺激。从这些研究中获得的结果 应提供有关腺苷分子功能的新信息 心肌中的受体。此外，这些发现应该显著地 有助于我们对G蛋白分子机制的基本知识 心脏中偶联受体的交叉调节。

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.