Mechanism of action of a potent antiplatelet peptide, triflavin from Trimeresurus flavoviridis snake venom.
Triflavin, an antiplatelet peptide from Trimeresurus flavoviridis snake venom, inhibits aggregation of human platelets stimulated by a variety of agonists. However, triflavin does not affect the shape change and release reaction of platelets stimulated by thrombin and collagen. In this paper, we further investigate its effect on the intracellular events occurring after the activation of platelets. Triflavin does not inhibit the intracellular free calcium rise of Quin 2-AM loaded platelets stimulated by thrombin and it also has no significant effect on thromboxane B2 formation of platelets stimulated by thrombin. Triflavin does not affect the 3(H)-inositol monophosphate formation of the 3(H)-myoinositol loaded platelets. However, triflavin dose-dependently inhibits fibrinogen-induced aggregation and 125I-fibrinogen binding of ADP-stimulated platelets. In addition, triflavin dose-dependently blocks fibrinogen-induced aggregation of elastase-treated platelets. It is concluded that triflavin specifically inhibits fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex on platelet membrane surface without any inhibitory effect on the platelet-activation process.
Huang
T F
TF
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Sheu
J R
JR
Teng
C M
CM
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D002118:Calcium / Q000097:blood; D003435:Crotalid Venoms / Q000737:chemistry*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D010455:Peptides / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D003435:Crotalid Venoms; D007457:Iodine Radioisotopes; D010455:Peptides; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; C029748:Trimeresurus venoms; C070025:triflavin; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D002118:Calcium