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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4167-4175. Prepublished online as a Blood First Edition Paper on August 30, 2005; DOI 10.1182/blood-2005-04-1723. This Article Full Text (PDF) All Versions of this Article: 2005-04-1723v1 106/13/4167    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 Moraes, L. Articles by Perretti, M. Search for Related Content PubMed PubMed Citation Articles by Moraes, L. Articles by Perretti, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 27, 2005 Accepted August 3, 2005 Ligand specific glucocorticoid receptor activation in human platelets Leonardo Moraes, Mark J Paul-Clark, Alice Rickman, Roderick J Flower, Nicolas J Goulding, and Mauro Perretti* The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom * Corresponding author; email: m.perretti{at}qmul.ac.uk. Few studies have addressed the effects of classical anti-inflammatory glucocorticoids on platelet function. Here we report for the first time that human platelets contain the glucocorticoid receptor (GR) as identified by a combination of biochemical and functional techniques. Ligand binding studies revealed the presence of a high and low affinity binding site for [3H]-dexamethasone in platelets. The two GR ligands prednisolone and dexamethasone competed for [3H]-dexamethasone binding, as did the mineralocorticoid aldosterone. However, whilst prednisolone (1-10 µM) reduced adenosine diphosphate (ADP) (4 µM) and thromboxane A2 receptor agonist U46619 induced platelet aggregation (up to 75%), dexamethasone had no effect. The inhibition produced by prednisolone was reversed by pre-incubation with the GR antagonist mifepristone (10 µM; RU486), suggesting the functional importance of the ligand-receptor complex. In addition, prednisolone caused a marked (~50%) reduction in thromboxane B2 levels, whereas dexamethasone was without effect. The apparently anomalous binding data was clarified by the fact that washed platelets i) contained mineralocorticoid receptor, and that ii) it was associated with GR. Taken together our data suggests that platelet GR forms a heterodimeric complex with the mineralocorticoid receptor that is susceptible to differential activation by specific receptor ligands. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. E. Herrera-Galeano, D. M. Becker, A. F. Wilson, L. R. Yanek, P. Bray, D. Vaidya, N. Faraday, and L. C. Becker A Novel Variant in the Platelet Endothelial Aggregation Receptor-1 Gene Is Associated With Increased Platelet Aggregability Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1484 - 1490. [Abstract] [Full Text] [PDF] L. A. Moraes, K. E. Swales, J. A. Wray, A. Damazo, J. M. Gibbins, T. D. Warner, and D. Bishop-Bailey Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets Blood, May 1, 2007; 109(9): 3741 - 3744. [Abstract] [Full Text] [PDF] M. Perretti Glucocorticoids in innate immunity: more transactivation than transrepression! Blood, February 1, 2007; 109(3): 852 - 853. [Full Text] [PDF]

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