Centre for Nephrology, UCL Medical School, University College London London, UK.
Front Physiol. 2013 Aug 15;4:216. doi: 10.3389/fphys.2013.00216. eCollection 2013.
Purinergic signaling within the kidney is becoming an important focus in the study of renal health and disease. The effectors of ATP signaling, the P2Y and P2X receptors, are expressed to varying extents in and along the nephron. There are many studies demonstrating the importance of the P2Y2 receptor on kidney function, and other P2 receptors are now emerging as participants in renal regulation. The P2X4 receptor has been linked to epithelial sodium transport in the nephron and expression levels of the P2X7 receptor are up-regulated in certain pathophysiological states. P2X7 antagonism has been shown to ameliorate rodent models of DOCA salt-induced hypertension and P2X4 null mice are hypertensive. Interestingly, polymorphisms in the genetic loci of P2X4 and P2X7 have been linked to blood pressure variation in human studies. In addition to the increasing evidence linking these two P2X receptors to renal function and health, a number of studies link the two receptors in terms of physical associations between their subunits, demonstrated both in vitro and in vivo. This review will analyze the current literature regarding interactions between P2X4 and P2X7 and assess the potential impact of these with respect to renal function.
嘌呤能信号在肾脏中正在成为研究肾脏健康和疾病的一个重要焦点。ATP 信号的效应器，即 P2Y 和 P2X 受体，在肾单位中以及沿着肾单位表达程度不同。有许多研究表明 P2Y2 受体对肾功能的重要性，其他 P2 受体现在也被认为是肾脏调节的参与者。P2X4 受体已与肾单位中的上皮钠转运有关，而 P2X7 受体的表达水平在某些病理生理状态下上调。已经表明，P2X7 拮抗剂可改善 DOCA 盐诱导的高血压的啮齿动物模型，并且 P2X4 缺失的小鼠患有高血压。有趣的是，P2X4 和 P2X7 基因座中的遗传多态性与人类研究中的血压变化有关。除了越来越多的证据将这两个 P2X 受体与肾功能和健康联系起来之外，许多研究还从体外和体内两方面在其亚基之间的物理关联方面将这两个受体联系起来。这篇综述将分析关于 P2X4 和 P2X7 之间相互作用的现有文献，并评估这些相互作用对肾功能的潜在影响。
