Adenosine attenuates reperfusion injury following regional myocardial ischaemia.
Adenosine attenuates reperfusion injury following regional myocardial ischaemia.
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腺苷可减轻局部心肌缺血后的再灌注损伤。
DOI：
10.1093/cvr/27.1.9
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发表时间：
1993
影响因子：
10.8
通讯作者：
Edwin K. Jackson
中科院分区：
文献类型：
--
作者：
Mervyn B. Forman;Mervyn B. Forman;Mervyn B. Forman;Carlos E. Velasco;Edwin K. Jackson;Edwin K. Jackson;Edwin K. Jackson
腺苷是一种内源性心脏核苷，主要由三磷酸腺苷（ATP）降解产生。心脏不断释放腺苷，这与心肌代谢有关。心肌中有限的能量储备加上高代谢需求，要求心肌细胞持续供应氧气和底物，以维持正常的代谢和收缩功能。心肌中的高能磷酸盐储存是有限的，主要以 ATP 和磷酸肌酸的形式存在。 3 心肌缺血后，高能磷酸盐会迅速耗尽，导致 80% 的磷酸肌酸在局部缺血后几分钟内丢失，并在 15 分钟内丢失一半以上的 ATP。缺血期间 ATP 的持续利用与线粒体无法再磷酸化二磷酸腺苷 (ADP) 相关，导致 ADP 和单磷酸腺苷 (AMP) 的积累。AMP 通过主要存在于细胞胞质部分的 5-核苷酸酶代谢为腺苷，腺苷在心肌细胞和间质中脱氨基为肌苷。 5 一旦 AMP 降解为腺苷，核苷转运系统就会促进缺血心肌细胞中腺苷和肌苷等核苷分子的损失。 5 由于这些化合物的快速冲洗，再灌注时会发生包括腺苷在内的腺嘌呤核苷酸的进一步耗尽。腺苷的作用主要由细胞外膜嘌呤能 1 型 (PI) 受体或通过非受体机制（例如补充心肌核苷酸库）介导。介导腺苷作用的细胞外 PI 受体被分类为 AI 或 A：并且主要存在于分别为心肌和冠状动脉血管系统。 AI和A的亚型？受体已被提出，并且对于开发用于治疗用途的更特异性激动剂可能具有重要意义。调节性 G 蛋白参与 A. 和 AI 的信号转导
Adenosine is an endogenous cardiac nucleoside produced primarily from the degradation of adenosine triphosphate (ATP).'A continual release of adenosine occurs from the heart which is related to myocardial metabolism. The limited energy reserves in the myocardium coupled with a high metabolic demand require there to be a constant supply of oxygen and substrates to myocardial cells to maintain normal metabolic and contractile function.''High energy phosphate stores in the myocardium are limited and exist predominantly in the form of ATP and creatine phosphate. 3 Following myocardial ischaemia, rapid depletion of high energy phosphate occurs, such that 80% of creatine phosphate is lost within minutes of re ional ischaemia and more than half the ATP by 15 minutes. Continual utilisation of ATP during ischaemia, associated with the inability of the mitochondria to rephosphorylate adenosine diphosphate (ADP), results in the accumulation of ADP and adenosine monophosphate (AMP).'AMP is metabolised via the enzyme 5-nucleotidase, found predominantly in the cytosolic fraction of the cell, to adenosine, which is deaminated to inosine both in the myocardial cell and in the interstitium. 5 Once AMP is degraded to adenosine, nucleoside transport systems facilitate the loss of nucleoside molecules such as adenosine and inosine from ischaemic myocardial cells. 5 Further depletion of adenine nucleotides including adenosine occurs with reperfusion due to rapid washout of these compounds.The effects of adenosine are mediated predominantly by extracellular membrane purinergic type 1 (PI) receptors or through a non-receptor mechanism such as replenishment of the myocardial nucleotide pool.'The extracellular PI receptors that mediate the effects of adenosine are classified as AI or A: and are found predominantly in the myocardium and coronary vasculature, respectively. Subtypes of the AI and A? receptor have been proposed and may have significance regarding the development of more specific agonists for therapeutic use. Regulatory G proteins are involved in the signal transduction for both the A. and AI