Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria, Instituto Universitario de Investigación en Neuroquímica, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Universidad Complutense Madrid, 28040, Madrid, Spain.
Adv Exp Med Biol. 2017;1051:139-168. doi: 10.1007/5584_2017_91.
The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y and P2Y. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y receptors but with unique features and roles. The P2RY12-14 genes all reside on human chromosome 3 at 3q25.1 and their strong sequence homology supports their evolutionary origin through gene duplication. Polymorphisms of P2Y receptors have been reported in different human populations, yet their consequences remain unknown. The P2Y receptor is versatile in its signalling, extending beyond the canonical signalling of a Gi-coupled receptor. Not only can it couple to different G proteins (Gs/Gq) but the P2Y receptor can also trigger several intracellular pathways related to the activation of MAPKs (mitogen-activated protein kinases) and the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 axis. Moreover, the availability of P2Y receptor knockout mice has highlighted the specific functions in which it is involved, mainly in the regulation of cholesterol and glucose metabolism, bone homeostasis and aspects of central nervous system function like pain transmission and neuroprotection. This review summarizes our current understanding of this elusive receptor, not only at the pharmacological and molecular level but also, in terms of its signalling properties and specific functions, helping to clarify the involvement of P2Y receptors in pathological situations.
核苷酸 P2Y 受体在不同组织中的分布表明，它们在许多生理和病理条件下发挥着关键作用。P2Y 是最新鉴定的 P2Y 受体之一，是 Gi 偶联 P2Y 受体亚家族的新成员，对 ADP 有反应，与 P2Y 和 P2Y 一起。药理学研究引起了人们对这种新的 ADP 受体的关注，其药理学与 P2Y 受体重叠，但具有独特的特征和作用。P2RY12-14 基因均位于人类 3 号染色体 3q25.1 上，其强序列同源性支持其通过基因复制起源于进化。已经在不同的人群中报道了 P2Y 受体的多态性，但它们的后果仍然未知。P2Y 受体在其信号传递中具有多功能性，超出了 Gi 偶联受体的典型信号传递。它不仅可以与不同的 G 蛋白（Gs/Gq）偶联，还可以触发与 MAPKs（丝裂原激活蛋白激酶）和磷脂酰肌醇 3-激酶/Akt/糖原合成酶激酶 3 轴激活相关的几种细胞内途径。此外，P2Y 受体敲除小鼠的可用性突出了其参与的特定功能，主要涉及胆固醇和葡萄糖代谢、骨稳态以及中枢神经系统功能的某些方面，如疼痛传递和神经保护。这篇综述总结了我们目前对这种难以捉摸的受体的理解，不仅在药理学和分子水平上，而且在其信号转导特性和特定功能方面，有助于阐明 P2Y 受体在病理情况下的参与。
