Journal
BLOOD
Volume 102, Issue 7, Pages 2472-2481Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-03-0734
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL70683] Funding Source: Medline
Ask authors/readers for more resources
Prothrombinase activity was tested on thrombin- and SFLLRN-activated platelets treated with RO318220, a potent inhibitor of protein kinase C. RO318220 completely inhibited platelet dense and alpha-granule secretion at a concentration of 20 muM but had no effect on prothrombinase activity in the presence of excess factor Va (20 nM). This indicates that protein kinase C activity and agonist-initiated secretion are not necessary for the development of a procoagulant surface. Treatment with 75 to 150 muM RO318220 potentiated platelet-supported thrombin generation up to 280% of control platelets with no change in K-d (appFxa). Treated with increasing concentrations of RO318220, an increasing proportion of thrombin-stimulated platelets bound annexin V with decreasing binding sites per platelet. A lower mean forward scatter (FSC-H) of platelets treated with RO318220 suggested platelet vesiculation as a result of RO318220 treatment; however, 100 muM calpeptin pretreatment eliminated the decrease in FSC-H without affecting either the increase in platelets positive for annexin V binding, the decrease in binding sites per platelet, or the 3-fold increase in prothrombinase activity. Thus, RO318220 appears to increase prothrombinase activity by increasing platelet responsiveness to thrombin rather than by inducing platelet vesiculation. This suggests that RO318220 inhibits a signaling molecule within a negative regulatory pathway that governs platelet procoagulant surface changes. (C) 2003 by The American Society of Hematology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available