Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox
Antithrombotic effect of crotalin, a platelet membrane glycoprotein Ib antagonist from venom of Crotalus atrox
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DOI：
10.1182/blood.v91.5.1582.1582_1582_1589
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发表时间：
1998-03-01
期刊：
影响因子：
20.3
通讯作者：
Huang, TF
中科院分区：
文献类型：
--
作者：
Chang, MC;Lin, HK;Huang, TF
从响尾蛇（Crotalus atrox）蛇毒中分离纯化了一种分子量为30 kD的血小板糖蛋白Ib（GPIb）拮抗剂crotalin。Crotalin特异性地和剂量依赖性地抑制由利托那诱导的人洗涤血小板聚集，IC 50为2.4 μ g/ml。(83 nmol/L）。它也能有效抑制瑞斯托霉素诱导的富血小板血浆血小板聚集（IC 50，6.3 μ g/mL）。I-125-crotalin以可饱和和剂量依赖的方式与人血小板结合，kd值为3.2+/-0.1 x 10（-7）mol/L，其结合位点估计为58，632 +/-3，152/血小板。它的结合特异性抑制单克隆抗体，AP 1提出了对血小板GP 1b。Crotalin能显著延长低浓度凝血酶（0.03 U/mL）诱导的血小板聚集的潜伏期，并能抑制由瑞斯托康加血管性血友病因子（vWF）或凝血酶（0.03 U/mL）诱导的血小板血栓素B-2的形成。当以300 μ g/kg剂量静脉（IV）给予小鼠crotalin时，观察到尾部出血时间呈剂量依赖性延长。300 μ g/kg时，延长尾出血时间的作用持续4小时。此外，其在体内的抗血栓形成活性被证明是通过延长诱导富血小板血栓形成的潜伏期，通过照射荧光素钠处理的小鼠的肠系膜小静脉。当以100至300 μ g/kg IV给药时，crotalin剂量依赖性地延长了诱导富血小板血栓形成的时间间隔。总之，crotalin特异性抑制vWF诱导的血小板凝集的存在下，ristoclavin，因为crotalin选择性地结合到血小板表面受体-糖蛋白Ib，导致在封锁的相互作用vWF与血小板膜GP 1b。此外，crotalin是一种有效的抗血栓形成剂，因为它在体内明显阻断血小板栓的形成，（C）1998年由美国血液学会。
A potent platelet glycoprotein Ib (GPIb) antagonist, crotalin, with a molecular weight of 30 kD was purified from the snake venom of Crotalus atrox. Crotalin specifically and dose dependently inhibited aggregation of human washed platelets induced by ristocetin with IC50 Of 2.4 mu g/ml. (83 nmol/L). It was also active in inhibiting ristocetin-induced platelet aggregation of platelet-rich plasma (IC50, 6.3 mu g/mL). I-125-crotalin bound to human platelets in a saturable and dose-dependent manner with a kd value of 3.2+/-0.1 x 10(-7) mol/L, and its binding site was estimated to be 58,632+/-3,152 per platelet. Its binding was specifically inhibited by a monoclonal antibody, AP1 raised against platelet GPlb. Crotalin significantly prolonged the latent period in triggering platelet aggregation caused by low concentration of thrombin (0.03 U/mL), and inhibited thromboxane B-2 formation of platelets stimulated either by ristocetin plus von Willebrand factor (vWF), or by thrombin (0.03 U/mL). When crotalin was intravenously (IV) administered to mice at inn to 300 mu g/kg, a dose-dependent prolongation on tail bleeding time was observed. The duration of crotalin in prolonging tail bleeding time lasted for 4 hours as crotalin was given at 300 mu g/kg. In addition, its in vivo antithrombotic activity was evidenced by prolonging the latent period in inducing platelet-rich thrombus formation by irradiating the mesenteric venules of the fluorescein sodium-treated mice. When administered IV at 100 to 300 mu g/kg, crotalin dose dependently prolonged the time lapse in inducing platelet-rich thrombus formation. In conclusion, crotalin specifically inhibited vWF-induced platelet agglutination in the presence of ristocetin because crotalin selectively bound to platelet surface receptor-glycoprotein Ib, resulting in the blockade of the interaction of vWF with platelet membrane GPlb. In addition, crotalin is a potent antithrombotic agent because it pronouncedly blocked platelet plug formation in vivo, (C) 1998 by The American Society of Hematology.