Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King's College London, London, UK.
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Br J Pharmacol. 2024 Feb;181(4):580-592. doi: 10.1111/bph.16191. Epub 2023 Aug 2.
Platelets are necessary for maintaining haemostasis. Separately, platelets are important for the propagation of inflammation during the host immune response against infection. The activation of platelets also causes inappropriate inflammation in various disease pathologies, often in the absence of changes to haemostasis. The separate functions of platelets during inflammation compared with haemostasis are therefore varied and this will be reflected in distinct pathways of activation. The activation of platelets by the nucleotide adenosine diphosphate (ADP) acting on P2Y and P2Y receptors is important for the development of platelet thrombi during haemostasis. However, P2Y stimulation of platelets is also important during the inflammatory response and paradoxically in scenarios where no changes to haemostasis and platelet aggregation occur. In these events, Rho-GTPase signalling, rather than the canonical phospholipase Cβ (PLCβ) signalling pathway, is necessary. We describe our current understanding of these differences, reflecting on recent advances in knowledge of P2Y structure, and the possibility of biased agonism occurring from activation via other endogenous nucleotides compared with ADP. Knowledge arising from these different pathways of P2Y stimulation of platelets during inflammation compared with haemostasis may help therapeutic control of platelet function during inflammation or infection, while preserving essential haemostasis. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.
血小板对于维持止血功能是必要的。此外，血小板在宿主免疫反应对抗感染过程中对于炎症的传播也很重要。血小板的激活也会导致各种疾病病理中的炎症反应失调，而这种失调通常不会导致止血功能的改变。因此，血小板在炎症过程中的功能与止血过程中的功能是不同的，这将反映在不同的激活途径中。核苷酸二磷酸腺苷（ADP）作用于 P2Y 和 P2Y 受体激活血小板对于止血过程中血小板血栓的形成很重要。然而，P2Y 对血小板的刺激在炎症反应中也很重要，而且在没有止血和血小板聚集变化的情况下也是如此。在这些情况下，Rho-GTPase 信号通路而不是经典的磷脂酶 Cβ（PLCβ）信号通路是必需的。我们描述了我们对这些差异的理解，反映了最近在 P2Y 结构知识方面的进展，以及与 ADP 相比，通过其他内源性核苷酸激活可能发生的偏激动现象。与止血相比，炎症过程中血小板的 P2Y 刺激的这些不同途径所产生的知识可能有助于在炎症或感染期间对血小板功能进行治疗性控制，同时保持必要的止血功能。相关文章：本文是血小板嘌呤能受体和非血栓性疾病专题的一部分。要查看本部分的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.html。
