Department of Pharmacology and Toxicology, Pharma Center, University of Bonn, Bonn, Germany.
Biochem Pharmacol. 2021 May;187:114361. doi: 10.1016/j.bcp.2020.114361. Epub 2020 Dec 10.
Professor Geoffrey Burnstock proposed the concept of purinergic signaling via P1 and P2 receptors. P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular adenine and uracil nucleotides. Eight mammalian P2Y receptor subtypes have been identified. They are divided into two subgroups (P2Y, P2Y, P2Y, P2Y, and P2Y) and (P2Y, P2Y, and P2Y). P2Y receptors are found in almost all cells and mediate responses in physiology and pathophysiology including pain and inflammation. The antagonism of platelet P2Y receptors by cangrelor, ticagrelor or active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel reduces the ADP-induced platelet aggregation in patients with thrombotic complications of vascular diseases. The nucleotide agonist diquafosol acting at P2Y receptors is used for the treatment of the dry eye syndrome. Structural information obtained by crystallography of the human P2Y and P2Y receptor proteins, site-directed mutagenesis and molecular modeling will facilitate the rational design of novel selective drugs.
杰弗里·伯斯通（Geoffrey Burnstock）教授提出了通过 P1 和 P2 受体进行嘌呤能信号传递的概念。P2Y 受体是细胞外腺嘌呤和尿嘧啶核苷酸的 G 蛋白偶联受体（GPCR）。已经鉴定出八种哺乳动物 P2Y 受体亚型。它们分为两个亚群（P2Y、P2Y、P2Y、P2Y 和 P2Y）和（P2Y、P2Y 和 P2Y）。P2Y 受体几乎存在于所有细胞中，并介导生理和病理生理学中的反应，包括疼痛和炎症。血小板 P2Y 受体的拮抗剂坎格雷洛、替格瑞洛或噻吩吡啶化合物噻氯匹定、氯吡格雷和普拉格雷的活性代谢物可减少血小板在血管疾病血栓并发症患者中由 ADP 诱导的聚集。作用于 P2Y 受体的核苷酸激动剂二喹福司可用于治疗干眼症。通过人 P2Y 和 P2Y 受体蛋白的晶体学、定点诱变和分子建模获得的结构信息将有助于新型选择性药物的合理设计。
