Thrombin receptor activating peptide does not stimulate platelet procoagulant activity.
Platelets after challenge with alpha-thrombin alone, collagen alone or thrombin/collagen mixture were observed to increase the rate of activation of prothrombin by factor Xa in the presence of factor Va and calcium ion (platelet procoagulant activity) by a maximum of 25, 45 and 110 fold, respectively. The increase in platelet procoagulant activity due to these agonists has been described previously and arises from increased expression of phosphatidylserine on the platelet surface. When platelets were treated with the thrombin receptor activating peptide (TRAP) (SFLLRNPNDKYEPK), alone or in the presence of collagen or thrombin, no change in platelet procoagulant activity was observed at concentrations of TRAP sufficient to cause increased intracellular calcium levels and protein phosphorylation in a manner similar to that of thrombin. In addition, no increase in platelet procoagulant activity was seen upon treatment with TRAP in the presence of inactivated thrombin (PPACK-thrombin). These results suggest that the thrombin-mediated increase in procoagulant activity may be due to activation of a thrombin receptor distinct from the recently cloned G-protein-coupled receptor, or to other proteolytic events on the platelet surface.
Thrombosis Research Institute, London, United Kingdom.
C A
CA
Goodwin
C P
CP
Wheeler-Jones
V V
VV
Kakkar
J J
JJ
Deadman
K S
KS
Authi
M F
MF
Scully
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood; D015943:Factor Va / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011516:Prothrombin / Q000378:metabolism; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000494:pharmacology
D005456:Fluorescent Dyes; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C049925:fura-2-am; C072032:thrombin receptor peptide (42-55); D015943:Factor Va; D011516:Prothrombin; D013917:Thrombin; D015951:Factor Xa; D002118:Calcium; D016257:Fura-2