ADENOSINE AND CATECHOLAMINE INTERACTION IN THE HEART

腺苷和儿茶酚胺在心脏中的相互作用

• 批准号: 2215631
• 负责人: JAMES G DOBSON
• 金额: $ 23.26万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215631
• 关键词: adenosine; adenosinetriphosphatase; adenylate cyclase; beta adrenergic agent; calcium; catecholamines; cellular pathology; coronary disorder; cyclic AMP; fluorescent dye /probe; guinea pigs; heart circulation; heart contraction; heart failure; hormone regulation /control mechanism; isolation perfusion; laboratory rat; membrane transport proteins; oxygen consumption

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.

该项目的长期目标是调查 腺苷作为负反馈发挥作用的假设 哺乳动物中儿茶酚胺引起的反应的调节剂 心 一个具体的目的是揭示的重要性， 细胞外（间质）腺苷抗肾上腺素能作用 核苷在离体心脏中的作用 另一个具体目标 是研究腺苷调节细胞内 成人原代培养的心室肌细胞的钙， 细胞内钙敏感荧光指示剂。 最后也是 最重要的是旨在调查 膜生化机制，腺苷， 与其抑制性受体的相互作用， 心肌细胞中的抗肾上腺素能作用。 最后一个系列 研究培养的心室肌细胞和心室肌细胞 将使用膜。 从中获得的知识 项目应有助于显着的生理 腺苷抗肾上腺素能作用的特征 正常工作的心脏。 新知识还应该提供 深入了解调节心肌细胞的机制， 收缩状态在衰竭和缺氧的心脏中改变， 如在心脏和冠状动脉疾病的情况下。