Gibbins Jonathan M
Institute for Cardiovascular & Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading, Berkshire, UK.
Atherosclerosis. 2009 Sep;206(1):1-7. doi: 10.1016/j.atherosclerosis.2008.12.010. Epub 2008 Dec 14.
Soluble factors such as ADP and thromboxane (TX) A(2) that are secreted or released by platelets at sites of tissue injury, mediate autocrine and paracrine regulation of platelet function, resulting in rapid localised thrombus formation. The suppression of platelet function, particularly through targeting such secondary regulatory mechanisms, that serve to 'fine-tune' the platelet response, has proven effective in the prevention of inappropriate platelet activation that results in thrombosis. The most commonly used anti-platelet approaches (ADP receptor antagonism or inhibition of TXA(2) synthesis), however, lack efficacy in many patients, suggesting the existence of additional uncharacterised mechanisms for the regulation of platelet function. Recent data, which form a focus of this review, have identified peripheral tachykinin peptide family members, such as substance P and the newly identified endokinins, as physiologically important positive feedback regulators of platelet function. The actions of tachykinins that are released from platelets during activation are mediated by the neurokinin-1 receptor. Initial analysis of the role of this receptor in platelet thrombus formation, and thrombosis in the mouse, indicate this to be a promising new target for the development of anti-thrombotic drugs.
诸如二磷酸腺苷（ADP）和血栓素（TX）A2等可溶性因子，由血小板在组织损伤部位分泌或释放，介导血小板功能的自分泌和旁分泌调节，导致快速局部血栓形成。抑制血小板功能，特别是通过靶向这种用于“微调”血小板反应的二级调节机制，已被证明在预防导致血栓形成的不适当血小板活化方面是有效的。然而，最常用的抗血小板方法（ADP受体拮抗或抑制TXA2合成）在许多患者中缺乏疗效，这表明存在其他未被表征的血小板功能调节机制。作为本次综述重点的最新数据已确定外周速激肽肽家族成员，如P物质和新发现的内激肽，是血小板功能生理上重要的正反馈调节因子。活化过程中从血小板释放的速激肽的作用由神经激肽-1受体介导。对该受体在小鼠血小板血栓形成和血栓形成中的作用的初步分析表明，这是抗血栓药物开发的一个有前景的新靶点。
