Antithrombotic Effect of Crotalin, a Platelet Membrane Glycoprotein Ib Antagonist From Venom of Crotalus atrox

摘要: A potent platelet glycoprotein Ib (GPIb) antagonist, crotalin, with a molecular weight of 30 kD was purified from the snake venom Crotalus atrox. Crotalin specifically and dose dependently inhibited aggregation human washed platelets induced by ristocetin IC50 2.4 μg/mL (83 nmol/L). It also active in inhibiting ristocetin-induced platelet-rich plasma (IC50, 6.3 μg/mL). 125I-crotalin bound to saturable dose-dependent manner kd value 3.2 ± 0.1 × 10−7 mol/L, its binding site estimated be 58,632 3,152 per platelet. Its monoclonal antibody, AP1 raised against GPIb. significantly prolonged latent period triggering caused low concentration thrombin (0.03 U/mL), thromboxane B2formation stimulated either plus von Willebrand factor (vWF), or U/mL). When crotalin intravenously (IV) administered mice at 100 300 μg/kg, prolongation on tail bleeding time observed. The duration prolonging lasted for 4 hours as given μg/kg. In addition, vivo antithrombotic activity evidenced inducing thrombus formation irradiating mesenteric venules fluorescein sodium-treated mice. IV lapse formation. conclusion, vWF-induced agglutination presence because selectively surface receptor-glycoprotein Ib, resulting blockade interaction vWF membrane is agent it pronouncedly blocked plug vivo.