Document Detail


Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells.
MedLine Citation:
PMID:  1939654     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that platelets become unresponsive to agonists when stimulated in combined suspension with aspirin-treated human umbilical vein endothelial cells. Inhibition occurred concomitant with metabolism of platelet-derived endoperoxides to prostacyclin by endothelial cells. We now demonstrate that if aspirin-treated platelets which fully respond to appropriate doses of agonists are exposed to aspirin-treated endothelial cells, they remain unresponsive despite absence of prostacyclin. Platelet inhibition is due in large part to ecto-ADPase activity on the endothelial cells. This was established by incubating aspirin-treated endothelial cells with 14C-ADP. Radio-thin layer chromatography and aggregometry demonstrated that 14C-ADP and induction of platelet activation decreased rapidly and concurrently. AMP accumulated transiently, was further metabolized to adenosine, and deaminated to inosine. The apparent Km of the endothelial cell ADPase was 33-42 microM and the Vmax 17-43 nmol/min per 10(6) cells, values in the range of antithrombotic potential. Thus, at least three complementary systems in human endothelial cells control platelet responsiveness: a cell-associated, aspirin-insensitive ADPase which functions in parallel with fluid phase autacoids such as the aspirin-inhibitable eicosanoids, and the aspirin-insensitive endothelium-derived relaxing factor.
Authors:
A J Marcus; L B Safier; K A Hajjar; H L Ullman; N Islam; M J Broekman; A M Eiroa
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  88     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1991 Nov 
Date Detail:
Created Date:  1991-12-13     Completed Date:  1991-12-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1690-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Department of Veterans Affairs Medical Center, New York, NY 10010.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / physiology
Apyrase / analysis,  physiology*
Aspirin / pharmacology*
Blood Platelets / drug effects*,  physiology
Endothelium, Vascular / physiology*
Humans
Nitric Oxide / physiology
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / pharmacology*
Thrombin / pharmacology
Grant Support
ID/Acronym/Agency:
HL-18828-16/HL/NHLBI NIH HHS; HL-46403/HL/NHLBI NIH HHS; HL-47073-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 10102-43-9/Nitric Oxide; 50-78-2/Aspirin; 58-64-0/Adenosine Diphosphate; EC 3.4.21.5/Thrombin; EC 3.6.1.5/Apyrase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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