CARDIAC ADENOSINE RECEPTORS

这个项目继续测试的假设，腺苷是 冠状动脉血流和心脏功能的生理调节剂， 侧重于激动剂的构效关系（SAR）， 心房和冠状动脉的腺苷受体的拮抗剂 动脉 该研究计划要求开发新的 新的2-取代的和2，6-二取代的N-乙基腺苷-5 ′-糖醛酰胺， 其中一些将适合于放射性标记、光亲和性 放射性标记和作为亲和层析的配体。 生物 研究将使用腺苷类似物的SAR来标测心脏心房 受体介导的负性变时和变力作用 腺苷并将这些受体与真正的A1腺苷进行比较 受体。 其他的类似物用于绘制嘌呤C-2的拓扑图， 区域和核糖结构域的A2受体在培养的细胞系， 看看这些体外系统如何预测体内冠状血管活性。 诸如此类的研究为药物的合理设计提供了依据 利用抗心律失常、抗凝血和血管扩张的特性 腺苷。

This project continues tests of the hypothesis that adenosine is a physiological regulator of coronary blood flow and cardiac performance, focusing on the structure-activity relationships (SAR) of agonists and antagonists at the adenosine receptors of the cardiac atria and of coronary arteries. The research plan calls for the development of new systheses of novel 2-substituted and 2,6-disubstituted N-ethyl adenosine-5'-uronamides, some of which will be suitable for radiolabelling, photoaffinity radiolabelling and as ligands for affinity chromatography. Biological studies will use the SARs of adenosine analogs to map the cardiac atrial receptors which mediate the negative chronotropic and inotropic effects of adenosine and to compare these receptors with authentic A1 adenosine receptors. Other analgos serve to map the topography of the purine C-2 region and ribose domain of the A2 receptors in cultured cell lines and to see how well these in vitro systems predict coronary vasoactivity in vivo. Studies such as these provide the basis for the rational design of drugs that exploit the antiarrythmic, anticoagulant and vasodilatory properties of adenosine.