Human gamma-thrombin: lack of correlation between a platelet functional response and glycoprotein V hydrolysis.
The ability of purified human gamma-thrombin to stimulate platelet function was related to its capacity to degrade GP V. Compared to alpha-thrombin, much greater amounts of gamma-thrombin were required to induce platelet aggregation; and this also applied to secretion from dense bodies, alpha-granules and lysosomal granules. Platelet stimulation by gamma-thrombin was additionally characterized by the presence of a lag-phase. Platelets with 3H-labelled surface glycoproteins showed the same functional response to both alpha- and gamma-thrombin as unlabelled platelets. But while threshold levels of alpha-thrombin induced little GP V hydrolysis confirming McGowan et al. (1), amounts of gamma-thrombin which induced substantial degradation (e.g. 8.3 nM degraded 36% of platelet GP V in 3 min) were unable to sustain either platelet aggregation or secretion. These results suggest that protein-binding regions remote from the catalytic site of alpha-thrombin are more important for platelet activation than GP V hydrolysis. They also provide further support to the argument that GP V hydrolysis may not be the essential trigger of platelet activation by thrombin.
Jandrot-Perrus
M
M
Unité 150 INSERM, Hôpital Lariboisière, Paris, France.
Guillin
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MC
Nurden
A T
AT
D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*
D010980:Platelet Membrane Glycoproteins; D013917:Thrombin