ADENOSINE AND CATECHOLAMINE INTERACTION IN THE HEART

这项计划的长期目标是调查 腺苷起负反馈作用的假说 儿茶酚胺调节因子在哺乳动物中引起的反应 心。一个具体的目标是揭示 细胞外(间质)腺苷在抗肾上腺素能作用中的作用 核苷在分离的工作心脏中的作用。另一个具体目标 是为了研究腺苷调节细胞内的能力 成年原代培养的心室肌细胞钙离子的研究 细胞内钙敏感荧光指示剂。最后，还有 最重要的是旨在调查 腺苷的膜生化机制 与其抑制性受体的相互作用，体现了它的 心肌细胞中的抗肾上腺素能作用。在上一个系列中 培养的心室肌细胞和心室肌细胞 将利用膜。从这一过程中获得的知识 项目应该对生理学做出重大贡献 腺苷的抗肾上腺素能作用的特性 正常的工作心脏。新的知识也应该提供 洞察心肌调节机制的方式 在衰竭和缺氧的心脏中，收缩状态会改变，如 在心脏病和冠状动脉疾病的情况下。

The long-term objective of this project is to investigate the hypothesis that adenosine functions as a negative-feedback regulator of catecholamine-elicited responses in the mammalian heart. One specific aim is to reveal the importance of extracellular (interstitial) adenosine in the antiadrenergic actions of the nucleoside in isolated working hearts. Another specific aim is to investigate the ability of adenosine to modulate intracellular calcium of adult primary cultured ventricular myocytes using an intracellular calcium sensitive fluorescent indicator. Finally, and of primary importance are the studies designed to investigate the membrane biochemical mechanisms by which adenosine, upon interaction with its inhibitory receptor, manifests its antiadrenergic actions in the myocardial cell. For the last series of studies cultured ventricular myocytes and ventricular membranes will be utilized. The knowledge gained from this project should contribute significantly to the physiological characterization of the antiadrenergic action of adenosine in the normal working heart. The new knowledge should also provide insight into the way in which mechanisms regulating myocardial contractile state are altered in the failing and hypoxic heart, such as in conditions of cardiac and coronary artery disease.