Lambrecht G
Department of Pharmacology, Biocentre Niederursel, University of Frankfurt, Main, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2000 Nov;362(4-5):340-50. doi: 10.1007/s002100000312.
P2X receptors are nucleotide-gated cation channels composed of homomeric or heteromeric assemblies of three subunits. In the past 7 years, an extended series (P2X1-7) of P2X subunits has been cloned from vertebrate tissues. In this rapidly expanding field, one of the main current challenges is to relate the cloned P2X receptor subtypes to the diverse physiological responses mediated by the native P2X receptors. However, the paucity of useful ligands, especially subtype-selective agonists and antagonists as well as radioligands, acts as a considerable impediment to progress. Most of the ligands available are highly limited in terms of their kinetics of action, receptor-affinity, subtype-selectivity and P2X receptor-specificity. Their suspected ability to be a substrate for ecto-nucleotidases or to inhibit these enzymes also complicates their use. A number of new antagonists at P2X receptors have recently been described which to some degree are more potent and more selective than earlier antagonists like suramin or pyridoxal-5'-phosphate-6-azophenyl 2',4'-disulfonate (PPADS). This work moves us closer to the ideal goal of classifying the recombinant and native P2X receptor subtypes on the basis of antagonist profiles. This review begins with a brief account of the current status of P2X receptors. It then focuses on the pharmacological properties of a series of key P2 receptor agonists and antagonists and will finish with the discussion of some related therapeutic possibilities.
P2X受体是由三个亚基的同聚体或异聚体组装而成的核苷酸门控阳离子通道。在过去7年中，已从脊椎动物组织中克隆出一系列（P2X1 - 7）扩展的P2X亚基。在这个迅速发展的领域，当前的主要挑战之一是将克隆的P2X受体亚型与天然P2X受体介导的多种生理反应联系起来。然而，缺乏有用的配体，尤其是亚型选择性激动剂、拮抗剂以及放射性配体，这对研究进展构成了相当大的阻碍。现有的大多数配体在作用动力学、受体亲和力、亚型选择性和P2X受体特异性方面都受到很大限制。它们被怀疑是胞外核苷酸酶的底物或能抑制这些酶，这也使得它们的使用变得复杂。最近已经描述了一些新的P2X受体拮抗剂，在某种程度上，它们比苏拉明或5'-磷酸吡哆醛-6-偶氮苯基2',4'-二磺酸盐（PPADS）等早期拮抗剂更有效、更具选择性。这项工作使我们更接近基于拮抗剂谱对重组和天然P2X受体亚型进行分类的理想目标。本综述首先简要介绍P2X受体的现状。然后重点讨论一系列关键P2受体激动剂和拮抗剂的药理特性，并将以一些相关治疗可能性的讨论作为结尾。
