Pathogenesis of a bleeding disorder characterized by platelet unresponsiveness to thromboxane A_2

以血小板对血栓素 A_2 无反应为特征的出血性疾病的发病机制

• 批准号: 09671101
• 负责人: FUSE Ichiro
• 金额: $ 1.79万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671101/
• 关键词: Platelets; Thromboxane A_2; Receptor; Platelet unresponsiveness to thrombxane A_2

We investigated the mutation of the thromboxane A_2 (TXA_2) receptor in six patients with platelet unresponsiveness to TXA_2, and found that all of the patients patients have the same abnormality of the TXR (Arg^<60> to Leu), although four patients are homozygous and two patients are heterozygous for this mutation. However, in the latter patients, TXA_2-induced IP_3 formation and Ca^<2+> mobilization were within normal limilts.These results suggest that this mutation is the only abnormality which has been found in this platelet disorder, and that, in patients with heterozygous for this mutation, the mutant type TXR suppress the wild-type receptor mediated platelet aggregation by the mechanism independent of phospholipase C.

本文对6例血小板对血栓素A_2（TXA_2）无反应性患者的TXA_2受体突变进行了研究，发现所有患者的TXA_2受体（Arg <60>→ Leu）均异常，其中4例为纯合型，2例为杂合型。而后者TXA_2诱导的IP_3形成和Ca^&lt;2+&gt;动员均在正常范围内，提示该突变是该血小板疾病中唯一的异常，在该突变杂合子患者中，突变型TXR通过独立于磷脂酶C的机制抑制野生型受体介导的血小板聚集。

项目成果

Fuse I: "Pathogenetic analysis of a platelet disorder characterized by the absence of thromboxane A2-induced platelet aggregation" Niigata Medical Journal. 111. 676-682 (1997)

Fuse I：“以缺乏血栓素 A2 诱导的血小板聚集为特征的血小板疾病的病理遗传学分析”《新泻医学杂志》。