Inhibition of coagulation and thrombin-induced platelet activities by a synthetic dodecapeptide modeled on the carboxy-terminus of hirudin.
Inhibition of coagulation and thrombin-induced platelet activities by a synthetic dodecapeptide modeled on the carboxy-terminus of hirudin.
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以水蛭素羧基末端为模型的合成十二肽抑制凝血和凝血酶诱导的血小板活性。
DOI：
10.1182/blood.v75.2.399.bloodjournal752399
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发表时间：
1990
期刊：
影响因子：
20.3
通讯作者：
J. Maraganore
中科院分区：
文献类型：
--
作者：
J. Jakubowski;J. Maraganore
一种模拟水蛭素残基53-64的合成酪氨酸硫酸化十二肽（BG 8865）被发现以剂量依赖性方式升高人血浆的活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）和凝血酶时间（TT）。最敏感的试验是TT，在2.2和4.1微克/毫升水蛭素肽时，TT分别延长2和3倍。在羊抗人抗凝血酶III抗体存在的情况下，通过APTT监测，硫酸化十二肽对抗凝血酶III没有依赖性，并且其活性不会被血小板释放物或血小板因子4中和。在凝血酶诱导的血小板活化的研究中，发现水蛭素肽阻断聚集、5-羟色胺释放和血栓素A2生成。在凝血酶浓度为0.25 U/mL时，抑制血小板聚集的IC 50（导致50%抑制的浓度）为0.72微克/mL肽。TXA_2生成和5-羟色胺释放的抑制与聚集的抑制密切相关。使用来自临床记录的肝素诱导的血小板减少症患者的血小板，发现抗凝剂量的肝素可诱导血小板聚集和血栓素A2生成。与此形成鲜明对比的是，抗凝剂等效剂量的水蛭素肽对患者血小板没有影响，这可以通过缺乏血小板聚集和血栓素A2生成来证明。这些数据提供了令人信服的体外证据，表明水蛭素肽具有优于肝素的几个潜在优势，即有效抑制凝血酶诱导的血小板活性、辅助因子独立性、对内源性肝素中和因子不敏感以及明显缺乏直接或免疫介导的血小板刺激特性。
A synthetic, tyrosine-sulfated, dodecapeptide (BG8865) modeled on residues 53-64 of hirudin was found to elevate the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of human plasma in a dose-dependent manner. The most sensitive assay was the TT, which was prolonged 2 and 3 times control values at 2.2 and 4.1 micrograms/mL hirudin peptide, respectively. The sulfated dodecapeptide exhibited no dependency on antithrombin III as monitored by the APTT in the presence of sheep anti-human antithrombin III antibodies, and its activity was not neutralized by platelet releasates or platelet factor 4. In studies of thrombin-induced platelet activation, the hirudin peptide was found to block aggregation, serotonin release and thromboxane A2 generation. At thrombin concentrations of 0.25 U/mL, the IC50 (concentration resulting in 50% inhibition) for inhibition of platelet aggregation was 0.72 micrograms/mL peptide. Inhibition of TXA2 generation and serotonin release correlated closely with inhibition of aggregation. Using platelets from patients with clinically documented heparin-induced thrombocytopenia anticoagulant doses of heparin were found to induce platelet aggregation and thromboxane A2 generation. In sharp contrast, anticoagulant-equivalent doses of hirudin peptide had no effect on patient platelets, as evidenced by a lack of platelet aggregation and thromboxane A2 generation. These data provide compelling in vitro evidence that the hirudin peptide has several potential advantages over heparin, namely effective inhibition of thrombin-induced platelet activities, co-factor independence, insensitivity to endogenous heparin-neutralizing factors, and an apparent lack of direct or immune-mediated platelet stimulating properties.
血栓素和血清素受体拮抗剂对实验性冠状动脉狭窄狗冠状动脉内血小板沉积的影响。
影响因子：
37.8
作者：
Golino,P;Buja,LM;Ashton,JH;Kulkarni,P;Taylor,A;Willerson,JT
通讯作者：
Willerson,JT
血小板糖蛋白 Ib 的糖运载蛋白部分表达凝血酶的高亲和力和中等亲和力受体位点。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Harmon,JT;Jamieson,GA
通讯作者：
Jamieson,GA
在没有高亲和力凝血酶受体的情况下，凝血酶激活血小板。
影响因子：
2.9
作者：
Harmon,JT;Jamieson,GA
通讯作者：
Jamieson,GA