Burnstock G
University College Medical School, United Kingdom.
Curr Med Chem. 2015;22(7):819-44. doi: 10.2174/0929867321666140706130415.
Potent actions of ATP in the central nervous system (CNS) were reported in the late 1940's, but cloning and characterisation of receptors for purines and pyrimidines did not take place until the early 1990's, which identified seven P2X ion channel receptor subtypes, three of which form the cation channel as homomultimers or heteromultimers. P2X receptor subtypes are widely expressed in the CNS and their distribution is described in different regions. They function in synaptic cotransmission and neuromodulation, as well as in trophic signalling. ATP released from nerves and astroglial cells are predominantly involved in neuron-glial interactions. Purinergic signalling is involved in normal behaviour, including learning and memory, sleep and arousal, locomotor and feeding activities and cognition. P2X receptors participate in CNS pathophysiology, including injury, inflammation, Alzheimer's and Parkinson's diseases, multiple sclerosis and amyotrophic lateral sclerosis, depression and anxiety. P2X4 and P2X7 receptor antagonists are effective via microglia against neuropathic pain, while P2X3 receptor antagonists also reduce neuropathic pain, but via a different mechanism.
20世纪40年代末有报道称ATP在中枢神经系统（CNS）中具有强效作用，但直到20世纪90年代初才对嘌呤和嘧啶受体进行克隆和表征，确定了七种P2X离子通道受体亚型，其中三种以同多聚体或异多聚体形式形成阳离子通道。P2X受体亚型在中枢神经系统中广泛表达，其分布在不同区域有描述。它们在突触共传递和神经调节以及营养信号传导中发挥作用。从神经和星形胶质细胞释放的ATP主要参与神经元-胶质细胞相互作用。嘌呤能信号传导参与正常行为，包括学习和记忆、睡眠和觉醒、运动和进食活动以及认知。P2X受体参与中枢神经系统病理生理学，包括损伤、炎症、阿尔茨海默病和帕金森病、多发性硬化症和肌萎缩侧索硬化症、抑郁症和焦虑症。P2X4和P2X7受体拮抗剂通过小胶质细胞对神经性疼痛有效，而P2X3受体拮抗剂也能减轻神经性疼痛，但作用机制不同。
