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: 3337051
• 负责人: JAMES G DOBSON
• 金额: $ 13.61万
• 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 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337051
• 关键词: adenosine; adenylate cyclase; catecholamines; cyclic AMP; glycogenolysis; heart circulation; heart contraction; heart failure; heart metabolism; isolation perfusion; myocardial ischemia /hypoxia; oxygen consumption; ventricular hypertrophy

In the heart catecholamines produce an increase in contractility and glycogenolysis. Adenosine 3', 5'-monophosphate (cyclic AMP) appears to be important in mediating the mechanical and metabolic effects. Adenosine, another naturally occurring compound that is a potent coronary vasodilator and continually released from the myocardium, appears to play an important role in the regulation of coronary blood flow when demands for oxygen by the heart increase such as in the case with catecholamine stimulation. It is the purpose of this project to study the modulation of catecholamine-induced increases in cardiac contractility and glycogenolysis caused by endogenous myocardial adenosine. Earlier work supports the hypothesis that in addition to serving as an important vasoactive metabolite controlling coronary flow, adenosine serves as a negative-feedback regulator controlling the formation of cyclic AMP, activation of cyclic AMP-dependent protein kinase, adenylate cyclase and phosphorylase and enhanced contractile state elicited by catecholamines. The hypothesis will be investigated by studying the effects of endogenous adenosine on the metabolic and mechanical responses to catecholamine stimulation in an isolated working heart preparation of the guinea pig. The relationship between the endogenous adenosine concentration in extracellular fluid and coronary perfusates to the degree of the antiadrenergic effects caused by the nucleoside will be determined. The influence of adenosine on the binding of catecholamines to their membrane receptors will be investigated. The effect of endogenous adenosine on the metabolic and contractile responses elicited by other inotropic interventions including acetylcholine will be considered. To investigate the mechanism of action of adenosine further, the effects of the nucleoside on adenylate cyclase and phosphodiesterase, the enzymes responsible for cyclic AMP synthesis and degradation, respectively will be studied in addition to the effect of the nucleoside on the enzymes responsible for its own synthesis and degradation. The knowledge gained from these experiments should elucidate the mechanisms involving endogenous adenosine that regulate catecholamine induced changes in contractility and glycogenolysis in the normal, hypoxic and failing heart.

在心脏中，儿茶酚胺能增加心脏的收缩能力和 糖原分解。3‘，5’-一磷酸腺苷(CAMP)似乎是 在调节机械和代谢效应方面很重要。腺苷， 另一种天然存在的化合物，是一种有效的冠状动脉血管扩张剂 并不断地从心肌中释放，似乎扮演着重要的角色 在冠脉血流调节中的作用，当需要氧气时 心脏增加，如在儿茶酚胺刺激的情况下。它 本课题的目的就是研究调制信号的调制方式 儿茶酚胺引起的心肌收缩和糖原分解增加 由内源性心肌腺苷引起。早期的工作支持 假设除了作为重要的血管活性物质外 控制冠状动脉血流的代谢物，腺苷作为一种 控制环状AMP形成的负反馈调节器， 激活环磷酸腺苷依赖的蛋白激酶、腺苷环化酶和 儿茶酚胺引起的磷酸化和增强收缩状态。 这一假说将通过研究内源性的影响来检验。 腺苷对儿茶酚胺代谢和机械反应的影响 豚鼠离体心工作心脏的刺激性。 大鼠内源性腺苷浓度与血气分析的关系 细胞外液和冠状动脉灌流到的程度 核苷引起的抗肾上腺素能作用将被确定。这个 腺苷对儿茶酚胺与其膜结合的影响 将对受体进行研究。内源性腺苷对血管紧张素转换酶的影响 其他变力作用引起的代谢和收缩反应 将考虑包括乙酰胆碱在内的干预措施。去调查 腺苷的作用机制、核苷的作用 腺苷环化酶和磷酸二酯酶，这两种酶负责 环状AMP的合成和降解将分别在 除了核苷对负责其代谢的酶的影响 自身的合成和降解。从这些实验中获得的知识 应阐明涉及内源性腺苷的机制 调节儿茶酚胺引起的收缩和糖原分解的变化 在正常、缺氧和衰竭的心脏中。