Laboratório de Farmacologia e Neurobiologia, Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Department of Cardiology, Centro Hospitalar Tâmega e Sousa, 4564-007 Penafiel, Portugal.
Int J Mol Sci. 2020 Jul 15;21(14):5005. doi: 10.3390/ijms21145005.
Adenosine triphosphate (ATP) is a primordial versatile autacoid that changes its role from an intracellular energy saver to a signaling molecule once released to the extracellular milieu. Extracellular ATP and its adenosine metabolite are the main activators of the P2 and P1 purinoceptor families, respectively. Mounting evidence suggests that the ionotropic P2X4 receptor (P2X4R) plays pivotal roles in the regulation of the cardiovascular system, yet further therapeutic advances have been hampered by the lack of selective P2X4R agonists. In this review, we provide the state of the art of the P2X4R activity in the cardiovascular system. We also discuss the role of P2X4R activation in kidney and lungs vis a vis their interplay to control cardiovascular functions and dysfunctions, including putative adverse effects emerging from P2X4R activation. Gathering this information may prompt further development of selective P2X4R agonists and its translation to the clinical practice.
三磷酸腺苷（ATP）是一种原始的多功能自体活性物质，一旦释放到细胞外环境中，它就会从细胞内的能量储存器转变为信号分子。细胞外 ATP 和其腺苷代谢物分别是 P2 和 P1 嘌呤能受体家族的主要激活剂。越来越多的证据表明，离子型 P2X4 受体（P2X4R）在心血管系统的调节中发挥着关键作用，但由于缺乏选择性 P2X4R 激动剂，进一步的治疗进展受到了阻碍。在这篇综述中，我们提供了 P2X4R 在心血管系统中的最新研究进展。我们还讨论了 P2X4R 激活在肾脏和肺部中的作用，以及它们相互作用以控制心血管功能和功能障碍的情况，包括 P2X4R 激活所产生的潜在不良反应。收集这些信息可能会促使进一步开发选择性 P2X4R 激动剂，并将其转化为临床实践。
