William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
Biochem Pharmacol. 2012 May 15;83(10):1364-73. doi: 10.1016/j.bcp.2012.02.006. Epub 2012 Feb 16.
We have previously reported presence of the glucocorticoid (GC) receptor (GR) alpha on blood platelets, and its ability to modulate platelet aggregation when activated by the synthetic GC prednisolone (Pred). In the present study we investigated the effects of Pred on broader aspects of platelet functions to unveil novel non-genomic actions on this cell type. Using whole blood assay we demonstrated that Pred was the only GC able to inhibit platelet aggregation and platelet-monocyte interactions. This latter effect was due to regulation of platelets, not monocytes. We next examined the effects of Pred on physiological actions of platelets, observing inhibition of platelet adhesion and spreading on collagen under static conditions. Moreover Pred inhibited thrombus formation under flow, suggesting potential important effects in haemostasis and thrombosis. Pred was unable to regulate platelet reactivity under conditions where the effects of platelet-derived ADP and TxA₂ were blocked, suggesting that the GC targeted the activation-dependent component of the adhesion and aggregation response. The effects of Pred were not mediated through cyclic nucleotide signaling, but rather seemed to evolve around selective regulation of P2Y₁₂ ADP receptor signaling, intimating a novel mode of action. This study details the actions of Pred on platelets unveiling novel properties which could be relevant for this GC in controlling unwanted vascular and thrombotic diseases.
我们之前曾报道过糖皮质激素（GC）受体（GR）α存在于血小板中，并且当它被合成 GC 泼尼松龙（Pred）激活时，能够调节血小板聚集。在本研究中，我们研究了 Pred 对血小板功能更广泛方面的影响，以揭示这种细胞类型的新的非基因组作用。使用全血测定，我们证明 Pred 是唯一能够抑制血小板聚集和血小板-单核细胞相互作用的 GC。后一种作用是由于对血小板的调节，而不是单核细胞。接下来，我们研究了 Pred 对血小板生理作用的影响，观察到在静态条件下抑制血小板在胶原上的黏附和铺展。此外，Pred 抑制了流动状态下的血栓形成，表明在止血和血栓形成方面可能具有重要的潜在作用。当阻断血小板衍生的 ADP 和 TxA₂的作用时，Pred 不能调节血小板反应性，这表明 GC 靶向黏附和聚集反应的激活依赖性成分。Pred 的作用不是通过环核苷酸信号传导介导的，而是似乎围绕着对 P2Y₁₂ ADP 受体信号传导的选择性调节展开，暗示了一种新的作用模式。这项研究详细描述了 Pred 对血小板的作用，揭示了这种 GC 控制不需要的血管和血栓性疾病的新特性。
