Inhibition effects of KRDS, a peptide derived from lactotransferrin, on platelet function and arterial thrombus formation in dogs.
KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested for its effects in vitro on dog platelet function and in vivo on femoral arterial thrombus formation in dogs. KRDS inhibited ADP (8 microM)-induced platelet aggregation (IC50: 350 microM) and arachidonic acid (2 mM)-induced thromboxane B2 generation (IC50: 175 microM). In addition, the thrombin (0.2 U/ml)-induced serotonin release was inhibited by KRDS (IC50: 525 microM) and the expression of alpha-granule membrane protein (GMP-140) was also inhibited (IC50: 350 microM). The results show that KRDS is an inhibitor for platelet aggregation and secretion to which the inhibition is more potent. Meanwhile, in the experiment of arterial thrombosis in dogs, KRDS (5 microM/kg) and 125I-SZ-51 (a monoclonal antibody against GMP-140) were injected before operation and immediately after the thrombus formation, respectively. In the KRDS group, the weight of removed thrombi was reduced to 50% of that in controls and the radioactivity per mg of labeled thrombi to 33.3% while in blood the radioactivity increased 2 times that in controls at the 4th hour after the injection of 125I-SZ-51. The radioactivity ratio between removed thrombi and blood was only 16% of that in controls. These results indicate that KRDS can inhibit thrombus formation in vivo and is a promising antithrombotic agent.
Wu
G
G
Jiangsu Institute of Hematology, Thrombosis and Hemostasis Research Unit, Suzhou Medical College, China.
Ruan
C
C
Drouet
L
L
Caen
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007781:Lactoferrin / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D019007:P-Selectin; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D012701:Serotonin / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000378:metabolism
D005343:Fibrinolytic Agents; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C056549:KRDS peptide; D012701:Serotonin; D013929:Thromboxane B2; D007781:Lactoferrin