Richardt G, Waas W, Kranzhöfer R, Mayer E, Schömig A
Circ Res. 1987 Jul;61(1):117-23. doi: 10.1161/01.res.61.1.117.
The effects of exogenous and endogenous adenosine on exocytotic noradrenaline release were studied in rat hearts perfused in situ. Exocytotic release of endogenous noradrenaline (determined by high pressure liquid chromatography) was induced by electrical stimulation of the left cervicothoracic ganglion. Exogenous adenosine significantly reduced noradrenaline overflow from the heart. This suppression of noradrenaline overflow was not influenced by desipramine, indicating a mechanism independent from noradrenaline reuptake. The A1 subtype specific agonists cyclohexyladenosine and R-phenylisopropyladenosine had inhibitory effects at lower concentrations than adenosine and S-phenylisopropyladenosine, suggesting the relevance of presynaptic inhibitory adenosine receptors of the A1 subtype. Short ischemic periods of 3 minutes resulted in a marked coronary venous overflow of adenosine during reperfusion. This was accompanied by an inhibition of noradrenaline release evoked by nerve stimulation during ischemia. The adenosine antagonists theophylline and 8-phenyltheophylline prevented this suppression of noradrenaline release. Blockade of oxidative phosphorylation by cyanide in combination with glucose-free perfusion induced an increased formation of endogenous adenosine and suppression of stimulation-evoked noradrenaline overflow. Again, in the presence of the adenosine antagonists theophylline or 8-phenyltheophylline, this suppression was abolished. These results indicate that adenosine is a potent inhibitor of exocytotic noradrenaline release in the heart with relevance during conditions of increased endogenous adenosine formation such as myocardial ischemia.
在原位灌注的大鼠心脏中研究了外源性和内源性腺苷对去甲肾上腺素胞吐释放的影响。通过电刺激左颈胸神经节诱导内源性去甲肾上腺素的胞吐释放（通过高压液相色谱法测定）。外源性腺苷显著降低了心脏中去甲肾上腺素的溢出。去甲肾上腺素溢出的这种抑制不受地昔帕明的影响，表明其机制独立于去甲肾上腺素的再摄取。A1亚型特异性激动剂环己基腺苷和R-苯异丙基腺苷在比腺苷和S-苯异丙基腺苷更低的浓度下具有抑制作用，提示A1亚型突触前抑制性腺苷受体的相关性。3分钟的短暂缺血期导致再灌注期间腺苷显著的冠状静脉溢出。这伴随着缺血期间神经刺激诱发的去甲肾上腺素释放的抑制。腺苷拮抗剂茶碱和8-苯茶碱可防止这种去甲肾上腺素释放的抑制。氰化物联合无葡萄糖灌注阻断氧化磷酸化诱导内源性腺苷形成增加并抑制刺激诱发的去甲肾上腺素溢出。同样，在存在腺苷拮抗剂茶碱或8-苯茶碱的情况下，这种抑制被消除。这些结果表明，腺苷是心脏中去甲肾上腺素胞吐释放的有效抑制剂，在诸如心肌缺血等内源性腺苷形成增加的情况下具有相关性。
