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Prepublished online as a Blood First Edition Paper on June 12, 2003; DOI 10.1182/blood-2003-03-0734. This Article Full Text (PDF) All Versions of this Article: 2003-03-0734v1 102/7/2472    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by London, F. S Search for Related Content PubMed PubMed Citation Articles by London, F. S Social Bookmarking                   What's this? Submitted March 7, 2003 Accepted May 29, 2003 The protein kinase C inhibitor RO318220 potentiates thrombin-stimulated platelet supported prothrombinase activity Fredda S London* Sol Sherry Thrombosis Research Center and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA, USA * Corresponding author; email: flon{at}astro.temple.edu. 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 -granule secretion at a concentration of 20µM but had no effect on prothrombinase activity in the presence of excess factor Va (20nM). This indicates that protein kinase C activity and agonist-initiated secretion are not necessary for the development of a procoagulant surface. Treatment with 75-150 µM RO318220 potentiated platelet-supported thrombin generation up to 280% of control platelets with no change in KdappFXa. 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 µM 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.-L. Huang, J.-C. Cheng, A. Stern, J.-T. Hsieh, C.-H. Liao, and C.-P. Tseng Disabled-2 is a novel {alpha}IIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation J. Cell Sci., November 1, 2006; 119(21): 4420 - 4430. [Abstract] [Full Text] [PDF]

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