Ticlopidine Selectively Inhibits Human Platelet Responses to Adenosine Diphosphate
Ticlopidine Selectively Inhibits Human Platelet Responses to Adenosine Diphosphate
复制标题
噻氯匹定选择性抑制人血小板对二磷酸腺苷的反应
DOI：
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发表时间：
1991
影响因子：
6.7
通讯作者：
P. Mannucci
中科院分区：
文献类型：
--
作者：
M. Cattaneo;B. Akkawat;A. Lecchi;C. Cimminiello;A. Capitanio;P. Mannucci
对15名受试者口服噻氯匹定(250 mg，2次/d)前和服药后7天的血小板聚集和纤维蛋白原结合进行了研究。噻氯匹定明显抑制二磷酸腺苷(ADP)、过氧化内酯类似物U46619、胶原或低浓度凝血酶诱导的血小板聚集，但不抑制肾上腺素或高浓度凝血酶诱导的血小板聚集。噻氯匹定可抑制ADP、U46619或凝血酶(1U/ml)诱导的125I-纤维蛋白原结合。ADP清除剂apyrase或CP/CPK在体外加入到在噻氯匹定之前获得的血小板悬液中，引起与噻氯匹定相同的聚集和125I-纤维蛋白原结合抑制。噻氯匹定不能抑制ADP清除剂诱导的进一步的血小板聚集和125I-纤维蛋白原结合。给予噻氯匹定后，凝血酶或U46619可增加抗GPIIb/IIIa单抗7E3与血小板的结合率，而ADP不能。噻氯匹定对凝血酶或凝血酶+肾上腺素引起的凝块收缩无抑制作用，但对PGE_1诱导的血小板cAMP升高有抑制作用，但不能抑制肾上腺素的作用。噻氯匹定不改变福尔马林固定的血小板上3 H-ADP的高、低亲和力结合位点数及其Kd。这些发现表明，噻氯匹定选择性地抑制血小板对ADP的反应。
Summary Platelet aggregation and fibrinogen binding were studied in 15 individuals before and 7 days after the oral administration of ticlopidine (250 mg b.i.d.). Ticlopidine significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), the endoperoxide analogue U46619, collagen or low concentrations of thrombin, but did not inhibit platelet aggregation induced by epinephrine or high concentrations of thrombin. Ticlopidine inhibited 125I-fibrinogen binding induced by ADP, U46619 or thrombin (1 U/ml). The ADP scavengers apyrase or CP/CPK, added in vitro to platelet suspensions obtained before ticlopidine, caused the same pattern of aggregation and 125I-fibrihogen binding inhibition as did ticlopidine. Ticlopidine did not inhibit further platelet aggregation and 125I-fibrinogen binding induced in the presence of ADP scavengers. After ticlopidine administration, thrombin or U46619, but not ADP, increased the binding rate of the anti-GPIIb/IIIa monoclonal antibody 7E3 to platelets. Ticlopidine inhibited clot retraction induced by reptilase plus ADP, but not that induced by thrombin or by reptilase plus epinephrine, and prevented the inhibitory effect of ADP, but not that of epinephrine, on the PGE1-induced increase in platelet cyclic AMP. The number of high- and low-affinity binding sites for 3H-ADP on formalin-fixed platelets and their K d were not modified by ticlopidine. These findings indicate that ticlopidine selectively inhibits platelet responses to ADP.
聚集蛋白：介导激活的血小板 ADP 受体。
DOI：
10.1096/fasebj.4.5.2407587
发表时间：
1990
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Colman,RW
通讯作者：
Colman,RW