P2X7 受体通道：最新进展及 P2X7 拮抗剂在疾病模型中的应用。
The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease.
机构信息
School of Biological Sciences, University of Wollongong, New South Wales, Australia and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia (R.B., R.S.); and Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia (L.S.).
School of Biological Sciences, University of Wollongong, New South Wales, Australia and Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia (R.B., R.S.); and Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia (L.S.)
出版信息
Pharmacol Rev. 2014 Jul;66(3):638-75. doi: 10.1124/pr.113.008003.
The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but not exclusively, on immune cells. P2X7 activation results in a number of downstream events, including the release of proinflammatory mediators and cell death and proliferation. As such, P2X7 plays important roles in various inflammatory, immune, neurologic and musculoskeletal disorders. This review focuses on the use of P2X7 antagonists in rodent models of neurologic disease and injury, inflammation, and musculoskeletal and other disorders. The cloning and characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7, as well as recent observations regarding the gating and permeability of P2X7, are discussed. Furthermore, this review discusses polymorphic and splice variants of P2X7, as well as the generation and use of P2X7 knockout mice. Recent evidence for emerging signaling pathways downstream of P2X7 activation and the growing list of negative and positive modulators of P2X7 activation and expression are also described. In addition, the use of P2X7 antagonists in numerous rodent models of disease is extensively summarized. Finally, the use of P2X7 antagonists in clinical trials in humans and future directions exploring P2X7 as a therapeutic target are described.
P2X7 受体是一种三聚体 ATP 门控阳离子通道，主要（但并非排他性）存在于免疫细胞上。P2X7 的激活会导致许多下游事件，包括促炎介质的释放以及细胞死亡和增殖。因此，P2X7 在各种炎症、免疫、神经和肌肉骨骼疾病中发挥着重要作用。本综述重点介绍了 P2X7 拮抗剂在神经疾病和损伤、炎症以及肌肉骨骼和其他疾病的啮齿动物模型中的应用。本文讨论了人、大鼠、小鼠、豚鼠、狗和恒河猴 P2X7 的克隆和特性，以及最近关于 P2X7 的门控和通透性的观察结果。此外，本文还讨论了 P2X7 的多态性和剪接变体，以及 P2X7 敲除小鼠的产生和应用。最近关于 P2X7 激活下游新兴信号通路的证据，以及越来越多的 P2X7 激活和表达的负性和正性调节剂也进行了描述。此外，还广泛总结了 P2X7 拮抗剂在多种疾病的啮齿动物模型中的应用。最后，描述了 P2X7 拮抗剂在人类临床试验中的应用以及探索 P2X7 作为治疗靶点的未来方向。
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