Ticlopidine and Clopidogrel (SR 25990C) Selectively Neutralize ADP Inhibition of PGE1-Activated Platelet Adenylate Cyclase in Rats and Rabbits
Ticlopidine and Clopidogrel (SR 25990C) Selectively Neutralize ADP Inhibition of PGE1-Activated Platelet Adenylate Cyclase in Rats and Rabbits
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噻氯匹定和氯吡格雷 (SR 25990C) 选择性中和大鼠和兔中 PGE1 激活的血小板腺苷酸环化酶的 ADP 抑制
DOI：
10.1055/s-0038-1647481
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发表时间：
1991
影响因子：
6.7
通讯作者：
J. Maffrand
中科院分区：
文献类型：
--
作者：
G. Defreyn;Christian Gachet;P. Savi;F. Driot;Cazenave Jp;J. Maffrand
噻氯匹定及其有效类似物氯吡格雷是adp诱导的血小板聚集的有效抑制剂。为了提高对ADP选择性的理解，我们研究了这些化合物对pge1刺激的腺苷酸环化酶的影响，以及ADP、肾上腺素和凝血酶对该酶的抑制作用。这两种药物都没有改变pgej刺激大鼠或家兔血小板中cAMP的基础水平和cAMP积累动力学，这排除了对腺苷酸环化酶或环核苷酸磷酸二酯酶的任何直接影响。然而，在PGEr刺激的对照血小板中添加ADP后观察到的cAMP水平下降在处理动物的血小板中被抑制。相比之下，在兔血小板中，两种药物都不能阻止肾上腺素引起的cAMP水平下降。在大鼠血小板中，凝血酶抑制pgex诱导的cAMP升高，但这种作用似乎完全是由释放的ADP介导的。在这些条件下，发现氯吡格雷也能有效抑制凝血酶对血小板腺苷酸环化酶的作用并不奇怪。综上所述，噻氯匹定和氯吡格雷可选择性中和ADP对PGEr活化血小板腺苷酸环化酶的抑制作用。
Summary Ticlopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGEj-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGEr stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGEX-induced cAMP elevation but this effect seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGEr activated platelet adenylate cyclase in rats and rabbits.
血小板中 G 蛋白与刺激磷脂酶 C 并抑制腺苷酸环化酶的激动剂之间的相互作用。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brass,LF;Woolkalis,MJ;Manning,DR
通讯作者：
Manning,DR
糖蛋白 IIIa 和介导 ADP 诱导血小板活化的 100 kDa 膜蛋白（聚集蛋白）之间的区别。
影响因子：
3.9
作者：
Colman,RW;Figures,WR;Wu,QX;Chung,SY;Morinelli,TA;Tuszynski,GP;Colman,RF;Niewiarowski,S
通讯作者：
Niewiarowski,S
ADP 诱导的血小板形状变化和细胞质离子钙的动员是由血小板上不同的结合位点介导的：5-对氟磺酰基苯甲酰基腺苷是一种弱血小板激动剂。
影响因子：
20.3
作者：
Rao,AK;Kowalska,MA
通讯作者：
Kowalska,MA