von Lubitz D K
Department of Emergency Medicine, University of Michigan Medical Center, Ann Arbor 48109-0303, USA.
Eur J Pharmacol. 1999 Apr 23;371(1):85-102. doi: 10.1016/s0014-2999(99)00135-1.
Numerous studies have consistently shown that agonist stimulation of adenosine A1 receptors results in a significant reduction of morbidity and mortality associated with global and focal brain ischemia in animals. Based on these observations, several authors have suggested utilization of adenosine A1 receptors as targets for the development of clinically viable drugs against ischemic brain disorders. Recent advent of adenosine A1 receptor agonists characterized by lowered cardiovascular effects added additional strength to this argument. On the other hand, although cardioprotective, adenosine A3 receptor agonists proved severely cerebrodestructive when administered prior to global ischemia in gerbils. Moreover, stimulation of adenosine A3 receptors appears to reduce the efficacy of some of the neuroprotective actions mediated by adenosine A1 receptors. The review discusses the possible role of adenosine receptor subtypes (A1, A2, and A3) in the context of their involvement in the pathology of cerebral ischemia, and analyzes putative strategies for the development of clinically useful strategies based on adenosine and its receptors. It also stresses the need for further experimental studies before definitive conclusions on the usefulness of the adenosine concept in the treatment of brain ischemia can be made.
大量研究一致表明，激动剂刺激腺苷A1受体可显著降低动物全脑和局灶性脑缺血相关的发病率和死亡率。基于这些观察结果，几位作者建议将腺苷A1受体作为开发针对缺血性脑疾病的临床可行药物的靶点。最近出现的具有较低心血管效应的腺苷A1受体激动剂为这一观点增添了更多依据。另一方面，尽管腺苷A3受体激动剂具有心脏保护作用，但在沙土鼠全脑缺血前给药时，却被证明具有严重的脑损伤作用。此外，刺激腺苷A3受体似乎会降低一些由腺苷A1受体介导的神经保护作用的功效。这篇综述讨论了腺苷受体亚型（A1、A2和A3）在参与脑缺血病理过程中的可能作用，并分析了基于腺苷及其受体开发临床有用策略的假定策略。它还强调，在就腺苷概念在治疗脑缺血中的有用性得出明确结论之前，需要进行进一步的实验研究。
