Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
Neurochem Res. 2022 Dec;47(12):3543-3555. doi: 10.1007/s11064-022-03737-3. Epub 2022 Aug 30.
Several experimental studies have linked adenosine's neuroprotective role in cerebral ischemia. During ischemia, adenosine is formed due to intracellular ATP breakdown into ADP, further when phosphate is released from ADP, the adenosine monophosphate is formed. It acts via A1, A2, and A3 receptors found on neurons, blood vessels, glial cells, platelets, and leukocytes. It is related to various effector systems such as adenyl cyclase and membrane ion channels via G-proteins. Pharmacological manipulation of adenosine receptors by agonists (CCPA, ADAC, IB-MECA) increases ischemic brain damage in various in vivo and in vitro models of cerebral ischemia whereas, agonist can also be neuroprotective. Mainly, receptor antagonists (CGS15943, MRS1706) indicated neuroprotection. Later, various studies also revealed that the downregulation or upregulation of specific adenosine receptors is necessary during the recovery of cerebral ischemia by activating several downstream signaling pathways. In the current review, we elaborate on the dual roles of adenosine and its receptor subtypes A1, A2, and A3 and their involvement in the pathobiology of cerebral ischemic injury. Adenosine-based therapies have the potential to improve the outcomes of cerebral injury patients, thereby providing them with a more optimistic future.
已有几项实验研究将腺苷在脑缺血中的神经保护作用联系起来。在缺血期间，由于细胞内 ATP 分解为 ADP，进一步当 ADP 从磷酸盐释放时，形成腺苷单磷酸。它通过神经元、血管、神经胶质细胞、血小板和白细胞上的 A1、A2 和 A3 受体起作用。它通过 G 蛋白与各种效应系统（如腺苷酸环化酶和膜离子通道）相关。通过激动剂（CCPA、ADAC、IB-MECA）对腺苷受体进行药理学操作会增加各种体内和体外脑缺血模型中的缺血性脑损伤，而激动剂也可能具有神经保护作用。主要的受体拮抗剂（CGS15943、MRS1706）表明具有神经保护作用。后来，各种研究还表明，通过激活几种下游信号通路，在脑缺血恢复过程中，下调或上调特定的腺苷受体是必要的。在本综述中，我们详细阐述了腺苷及其受体亚型 A1、A2 和 A3 的双重作用及其在脑缺血损伤的病理生物学中的参与。基于腺苷的治疗方法有可能改善脑损伤患者的预后，从而为他们提供更乐观的未来。
