Jones Sarah, Tucker Katherine L, Sage Tanya, Kaiser William J, Barrett Natasha E, Lowry Philip J, Zimmer Andreas, Hunt Stephen P, Emerson Michael, Gibbins Jonathan M
School of Biological Sciences, University of Reading, UK.
Blood. 2008 Jan 15;111(2):605-12. doi: 10.1182/blood-2007-07-103424. Epub 2007 Sep 25.
Platelets play an important role in hemostasis, with inappropriate platelet activation being a major contributor to debilitating and often fatal thrombosis by causing myocardial infarction and stroke. Although current antithrombotic treatment is generally well tolerated and effective, many patients still experience cardiovascular problems, which may reflect the existence of alternative underlying regulatory mechanisms in platelets to those targeted by existing drugs. In this study, we define a role for peripherally distributed members of the tachykinin family of peptides, namely substance P and the newly discovered endokinins A and B that are present in platelets, in the activation of platelet function and thrombus formation. We have reported previously that the preferred pharmacologically characterized receptor for these peptides, the NK1 receptor, is present on platelets. Inhibition or deficiency of the NK1 receptor, or SP agonist activity, resulted in substantially reduced thrombus formation in vitro under arterial flow conditions, increased bleeding time in mice, and a decrease in experimentally induced thromboembolism. Inhibition of the NK1 receptor may therefore provide benefit in patients vulnerable to thrombosis and may offer an alternative therapeutic target.
血小板在止血过程中发挥着重要作用，血小板的不适当激活是导致心肌梗死和中风等使人衰弱且往往致命的血栓形成的主要因素。尽管目前的抗血栓治疗总体上耐受性良好且有效，但许多患者仍会出现心血管问题，这可能反映出血小板中存在现有药物所针对机制之外的其他潜在调节机制。在本研究中，我们确定了速激肽家族肽类物质（即血小板中存在的P物质以及新发现的内激肽A和B）在外周分布的成员在血小板功能激活和血栓形成中的作用。我们之前曾报道，这些肽类物质的药理学特征明确的首选受体——NK1受体存在于血小板上。NK1受体的抑制或缺乏，或P物质激动剂活性的缺乏，在动脉血流条件下可导致体外血栓形成显著减少、小鼠出血时间延长以及实验性诱导的血栓栓塞减少。因此，抑制NK1受体可能对易患血栓形成的患者有益，并可能提供一个替代治疗靶点。
