Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Department of Pharmacology and Toxicology, University of Aachen, Aachen, Germany.
Trends Cell Biol. 2018 May;28(5):392-404. doi: 10.1016/j.tcb.2018.01.005. Epub 2018 Feb 10.
ATP, which is released under pathological conditions and is considered a damage-associated molecular pattern (DAMP), activates P2X7 receptors (P2X7Rs), trimeric plasma membrane ion channels selective for small cations. P2X7Rs are partners in NOD-like receptor containing a pyrin (NLRP3) inflammasome activation and promoters of tumor cell growth. P2X7R overstimulation triggers the ATP-dependent opening of a nonselective plasma membrane pore, known as a 'macropore', which allows fluxes of large hydrophilic molecules. The pathophysiological functions of P2X7R are thought to be dependent on activation of this conductance pathway, yet its molecular identity is unknown. Recent reports show that P2X7R permeability to organic solutes is an early and intrinsic property of the channel itself. A better understanding of P2X7R-dependent changes in plasma membrane permeability will allow a rationale development of novel anti-inflammatory and anticancer drugs.
在病理条件下释放的三磷酸腺苷（ATP）被认为是一种损伤相关分子模式（DAMP），它可激活 P2X7 受体（P2X7Rs），即三聚物质膜阳离子选择性通道。P2X7Rs 是含 NOD 样受体含有 pyrin 结构域（NLRP3）炎症小体激活的伙伴，也是肿瘤细胞生长的促进剂。P2X7R 的过度刺激会触发 ATP 依赖性的非选择性质膜孔的打开，这种孔被称为“大孔”，允许大亲水分子的流动。P2X7R 的病理生理功能被认为依赖于该电导途径的激活，但它的分子身份尚不清楚。最近的报告表明，P2X7R 对有机溶质的通透性是通道本身的早期和内在特性。更好地了解 P2X7R 依赖性的质膜通透性变化将为新型抗炎和抗癌药物的合理开发提供依据。
