Ex-vivo and in-vivo antithrombotic effect of triflavin, an RGD-containing peptide.
Triflavin, an Arg-Gly-Asp-containing snake venom peptide, inhibits platelet aggregation through the blockade of fibrinogen binding to the activated platelets. It binds to fibrinogen receptors associated with the glycoprotein IIb/IIIa complex with a Kd value of 7 x 10(-8) M. In this study, we found that 125I-triflavin reached the maximal binding to human platelets within 5 min at 25 degrees C. In addition, when triflavin was intravenously administered at 1.0 mg kg-1 to rabbits, it reversibly impaired the platelet aggregation of platelet-rich plasma caused by ADP (20 microM) ex-vivo over 30 min. The platelet counts of the experimental rabbits remained unchanged. Triflavin was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at a dose of 2 micrograms g-1. Therefore, triflavin was proven to be an effective antithrombotic agent in preventing ADP-induced acute pulmonary thromboembolism in mice and impairing reversibly the platelet function of rabbits when given intravenously.
Sheu
J R
JR
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Huang
T F
TF
D000244:Adenosine Diphosphate; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D005340:Fibrinogen / Q000037:antagonists & inhibitors; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000188:drug therapy*; D011817:Rabbits
D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D036341:Intercellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C054194:trigramin; C070025:triflavin; D000244:Adenosine Diphosphate; D005340:Fibrinogen