Erlinge David
Department of Cardiology, Lund University, Skane University Hospital, Sweden.
Adv Pharmacol. 2011;61:417-39. doi: 10.1016/B978-0-12-385526-8.00013-8.
The purine- and pyrimidine-sensitive P2Y receptors belong to the large group of G-protein-coupled receptors that are the target of approximately one-third of the pharmaceutical drugs used in the clinic today. It is therefore not unexpected that the P2Y receptors could be useful targets for drug development. This chapter will discuss P2Y receptor-based therapies currently used, in development and possible future developments. The platelet inhibitors blocking the ADP-receptor P2Y(12) reduce myocardial infarction, stroke, and mortality in patients with cardiovascular disease. Clopidogrel (Plavix) was for many years the second most selling drug in the world. The improved P2Y(12) inhibitors prasugrel, ticagrelor, and elinogrel are now entering the clinic with even more pronounced protective effects. The UTP-activated P2Y(2) receptor stimulates ciliary movement and secretion from epithelial cells. Cystic fibrosis is a monogenetic disease where reduced chloride ion secretion results in a severe lung disease and early death. No specific treatment has been available, but the P2Y(2) agonist Denufosol has been shown to improve lung function and is expected to be introduced as treatment for cystic fibrosis soon. In preclinical studies, there are indications that P2Y receptors can be important for diabetes, osteoporosis, cardiovascular, and atherosclerotic disease. In conclusion, P2Y receptors are important for the health of humans for many diseases, and we can expect even more beneficial drugs targeting P2Y receptors in the future.
对嘌呤和嘧啶敏感的P2Y受体属于G蛋白偶联受体的大类，而G蛋白偶联受体是当今临床使用的约三分之一药物的作用靶点。因此，P2Y受体可能成为药物开发的有用靶点也就不足为奇了。本章将讨论目前正在使用、处于研发阶段以及未来可能的基于P2Y受体的疗法。阻断ADP受体P2Y(12)的血小板抑制剂可降低心血管疾病患者的心肌梗死、中风和死亡率。氯吡格雷（波立维）多年来一直是全球第二畅销药物。改进后的P2Y(12)抑制剂普拉格雷、替格瑞洛和依林格雷目前正在进入临床，具有更显著的保护作用。UTP激活的P2Y(2)受体可刺激上皮细胞的纤毛运动和分泌。囊性纤维化是一种单基因疾病，氯离子分泌减少会导致严重的肺部疾病和早期死亡。此前一直没有特效治疗方法，但P2Y(2)激动剂地纽福索已被证明可改善肺功能，预计很快将作为囊性纤维化的治疗药物推出。在临床前研究中，有迹象表明P2Y受体对糖尿病、骨质疏松症、心血管疾病和动脉粥样硬化疾病可能很重要。总之，P2Y受体对许多疾病患者的健康都很重要，我们预计未来会有更多针对P2Y受体的有益药物。
