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Abstract：
The known seven mammalian receptor subunits (P2X1-7) form cationic channels gated by ATP. Three subunits compose a receptor channel. Each subunit is a polypeptide consisting of two transmembrane regions (TM1 and TM2), intracellular N- and C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D structure and gating cycle of P2X receptors. The agonist-binding pocket is located at the intersection of two neighbouring subunits. In addition to the mammalian P2X receptors, their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2X receptor subtypes are not available, but medicinal chemistry supplied a range of subtype-selective antagonists, as well as positive and negative allosteric modulators. Knockout mice and selective antagonists helped to identify pathological functions due to defective P2X receptors, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).
摘要：
已知的七个哺乳动物受体亚基(P2X1-7)形成由ATP门控的阳离子通道。三个亚基组成一个受体通道。每个亚基是由两个跨膜区（TM1和TM2）组成的多肽，细胞内N-和C-末端，和庞大的细胞外环路。结晶允许鉴定P2X受体的3D结构和门控循环。激动剂结合口袋位于两个相邻亚基的交叉点。除了哺乳动物P2X受体，它们几乎没有结构相似性的原始配体门控对应物也已被克隆。P2X受体亚型的选择性激动剂不可用，但是药物化学提供了一系列亚型选择性拮抗剂，以及正负变构调节剂。基因敲除小鼠和选择性拮抗剂有助于鉴定由于P2X受体缺陷引起的病理功能，如男性不育（P2X1），听力损失（P2X2），疼痛/咳嗽（P2X3），神经性疼痛（P2X4），炎性骨丢失（P2X5），和错误的免疫反应（P2X7）。
