Inhibition of platelet hemostatic plug formation by trigramin, a novel RGD-peptide.
Trigramin, a cysteine rich, RGD (Arg-Gly-Asp)-containing peptide from Trimeresurus gramineus snake venom (Mr 7,500) has been previously reported to inhibit fibrinogen binding to ADP-activated platelets and platelet aggregation (disassociation constant 10(-8) M). The present study demonstrates that the infusion of trigramin (17-212 micrograms/100 g body wt) significantly prolonged the bleeding time of severed mesenteric arteries in hamsters (anesthetized with 65 mg/kg pentobarbital), whereas the infusion of RGDS (Arg-Gly-Asp-Ser, 0.45-1.0 mg/100 g body wt) failed to increase the bleeding time in this model. The bleeding time immediately returned to normal after cessation of trigramin infusion. The pattern of the disappearance of 125I-labeled trigramin from the circulation fit a two-compartment model with the half-life for the fast component between 0.7 and 2.0 min and with the half-life for the slow component between 31 and 105 min. It appeared that the kidney and liver are major routes of elimination of trigramin from the circulation. The ability of trigramin to prolong bleeding time, as well as its rapid disappearance from the circulation, indicates that this peptide may be a useful compound to transiently prevent the ability of platelets to form thromboemboli without impairing their long-term hemostatic function.
Cook
J J
JJ
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Huang
T F
TF
Rucinski
B
B
Strzyzewski
M
M
Tuma
R F
RF
Williams
J A
JA
Niewiarowski
S
S
D000818:Animals; D001760:Bleeding Time; D006224:Cricetinae; D005340:Fibrinogen / Q000037:antagonists & inhibitors*; D006487:Hemostasis / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins; D008638:Mesenteric Arteries; D009842:Oligopeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C054194:trigramin; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine