Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA.
Division of Molecular Biochemistry, Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
Int J Mol Sci. 2023 Apr 4;24(7):6709. doi: 10.3390/ijms24076709.
P2Y is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y in the cells of the immune system and the effect of P2Y activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.
P2Y 是一种 G 蛋白偶联受体，在 ADP 结合后被激活。鉴于其在血小板激活中的既定作用，抑制 P2Y 已被用作心血管疾病患者抗血小板聚集的治疗策略。然而，受体研究表明，P2Y 不仅在血小板和小胶质细胞中具有功能性表达，而且在免疫系统的其他细胞中也具有功能性表达，例如单核细胞、树突状细胞和 T 淋巴细胞。因此，进行了研究以调查靶向 P2Y 的治疗方法是否也可以改善炎症状态，如败血症、类风湿性关节炎、神经炎症、癌症、COVID-19、动脉粥样硬化和糖尿病相关炎症，在动物模型和人类受试者中。本综述报告了 P2Y 在免疫系统细胞中的表达以及 P2Y 激活和/或抑制在炎症状态下的作用。最后，我们将讨论研究该受体的主要问题和挑战，并提供如何克服这些问题的见解。
