Departamento de Farmacología, Facultad de Medicina y Odontología, Universidad de Valencia, 46010 Valencia, Spain.
CIBERehd, Valencia, Spain.
Int J Mol Sci. 2020 Nov 10;21(22):8454. doi: 10.3390/ijms21228454.
The P2X7 receptor (P2X7R) possesses a unique structure associated to an as yet not fully understood mechanism of action that facilitates cell permeability to large ionic molecules through the receptor itself and/or nearby membrane proteins. High extracellular adenosine triphosphate (ATP) levels-inexistent in physiological conditions-are required for the receptor to be triggered and contribute to its role in cell damage signaling. The inconsistent data on its activation pathways and the few studies performed in natively expressed human P2X7R have led us to review the structure, activation pathways, and specific cellular location of P2X7R in order to analyze its biological relevance. The ATP-gated P2X7R is a homo-trimeric receptor channel that is occasionally hetero-trimeric and highly polymorphic, with at least nine human splice variants. It is localized predominantly in the cellular membrane and has a characteristic plasticity due to an extended C-termini, which confers it the capacity of interacting with membrane structural compounds and/or intracellular signaling messengers to mediate flexible transduction pathways. Diverse drugs and a few endogenous molecules have been highlighted as extracellular allosteric modulators of P2X7R. Therefore, studies in human cells that constitutively express P2X7R need to investigate the precise endogenous mediator located nearby the activation/modulation domains of the receptor. Such research could help us understand the possible physiological ATP-mediated P2X7R homeostasis signaling.
P2X7 受体（P2X7R）具有独特的结构，其作用机制尚不完全清楚，它通过受体本身和/或附近的膜蛋白促进大离子分子向细胞内的通透性。高细胞外三磷酸腺苷（ATP）水平（在生理条件下不存在）是触发受体的必要条件，并有助于其在细胞损伤信号中的作用。其激活途径的不一致数据和在天然表达的人 P2X7R 中进行的少数研究促使我们回顾 P2X7R 的结构、激活途径和特定的细胞位置，以分析其生物学相关性。ATP 门控的 P2X7R 是一种同三聚体受体通道，偶尔是异三聚体，高度多态性，至少有九个人类剪接变体。它主要定位于细胞膜上，由于其延伸的 C 末端而具有特征性的可塑性，这赋予了它与膜结构化合物和/或细胞内信号信使相互作用的能力，以介导灵活的转导途径。多种药物和一些内源性分子已被强调为 P2X7R 的细胞外别构调节剂。因此，需要对持续表达 P2X7R 的人细胞进行研究，以研究位于受体激活/调节域附近的精确内源性介质。这种研究可以帮助我们了解可能的生理 ATP 介导的 P2X7R 动态平衡信号。
