SEARCH:   Advanced

Blood, 1 April 2004, Vol. 103, No. 7, pp. 2593-2600. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-09-3349. This Article Full Text (PDF) All Versions of this Article: 2003-09-3349v1 103/7/2593    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 Gambaryan, S. Articles by Walter, U. Search for Related Content PubMed PubMed Citation Articles by Gambaryan, S. Articles by Walter, U. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this? Submitted September 29, 2003 Accepted November 14, 2003 Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase Stepan Gambaryan, Joerg Geiger, Ulrike R Schwarz, Elke Butt, Antonija Begonja, Achim Obergfell, and Ulrich Walter* Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Wuerzburg, Germany * Corresponding author; email: uwalter{at}klin-biochem.uni-wuerzburg.de. Platelets play a key role in hemostasis through their ability to rapidly adhere to activated or injured endothelium, subendothelial matrix proteins, and other activated platelets. A strong equilibrium between activating and inhibiting processes is essential for normal platelet and vascular function, impairment of this equilibrium being associated with either thrombophilic or bleeding disorders. Both cGMP and cAMP have been established as crucial and synergistic intracellular messengers which mediate the effects of platelet inhibitors such as NO and PG-I2. However, it was recently suggested that a rapid cGMP / cGMP-dependent protein kinase (cGK)-mediated ERK phosphorylation promotes platelet activation. This hypothesis was examined here by evaluating established and proposed cGK activators / inhibitors with respect to their capacity to promote either platelet activation or inhibition. In particular, the regulatory role of cGK for ERK phosphorylation and thrombin-, thromboxane-, and vWF-induced platelet activation was investigated. The data obtained do not support the concept that cGK-mediated ERK phosphorylation promotes platelet activation but confirm the inhibitory role of cGK in platelet function. One explanation for these discrepancies is the novel finding that extracellular cGMP analogs potently and rapidly inhibit thrombin-, thromboxane-, and vWF-induced human platelet signaling and activation by a cGK-independent mechanism. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Does cGMP mediate platelet inhibition or stimulation? Wolfgang Siess Blood 2004 103: 2435-2436. [Full Text] [PDF] GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase Stuart J. Marshall, Yotis A. Senis, Jocelyn M. Auger, Robert Feil, Franz Hofmann, Gary Salmon, J. Thomas Peterson, Frank Burslem, and Steve P. Watson Blood 2004 103: 2601-2609. [Abstract] [Full Text] [PDF] This article has been cited by other articles: N. Valtcheva, P. Nestorov, A. Beck, M. Russwurm, M. Hillenbrand, P. Weinmeister, and R. Feil The Commonly Used cGMP-dependent Protein Kinase Type I (cGKI) Inhibitor Rp-8-Br-PET-cGMPS Can Activate cGKI in Vitro and in Intact Cells J. Biol. Chem., January 2, 2009; 284(1): 556 - 562. [Abstract] [Full Text] [PDF] M. L. Bilodeau and H. E. Hamm Regulation of Protease-Activated Receptor (PAR) 1 and PAR4 Signaling in Human Platelets by Compartmentalized Cyclic Nucleotide Actions J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 778 - 788. [Abstract] [Full Text] [PDF] M. Antl, M.-L. von Bruhl, C. Eiglsperger, M. Werner, I. Konrad, T. Kocher, M. Wilm, F. Hofmann, S. Massberg, and J. Schlossmann IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation Blood, January 15, 2007; 109(2): 552 - 559. [Abstract] [Full Text] [PDF] A. J. Begonja, J. Geiger, N. Rukoyatkina, S. Rauchfuss, S. Gambaryan, and U. Walter Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase Blood, January 15, 2007; 109(2): 616 - 618. [Abstract] [Full Text] [PDF] G. D. Lewis, C. Witzke, P. Colon-Hernandez, J. L. Guerrero, K. D. Bloch, and M. J. Semigran Sildenafil Improves Coronary Artery Patency in a Canine Model of Platelet-Mediated Cyclic Coronary Occlusion After Thrombolysis J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1471 - 1477. [Abstract] [Full Text] [PDF] F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion Physiol Rev, January 1, 2006; 86(1): 1 - 23. [Abstract] [Full Text] [PDF] A. J. Begonja, S. Gambaryan, J. Geiger, B. Aktas, M. Pozgajova, B. Nieswandt, and U. Walter Platelet NAD(P)H-oxidase-generated ROS production regulates {alpha}IIb{beta}3-integrin activation independent of the NO/cGMP pathway Blood, October 15, 2005; 106(8): 2757 - 2760. [Abstract] [Full Text] [PDF] C. Wagner, M. Russwurm, R. Jager, A. Friebe, and D. Koesling Dimerization of Nitric Oxide-sensitive Guanylyl Cyclase Requires the {alpha}1 N Terminus J. Biol. Chem., May 6, 2005; 280(18): 17687 - 17693. [Abstract] [Full Text] [PDF] J. Schultess, O. Danielewski, and A. P. Smolenski Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets Blood, April 15, 2005; 105(8): 3185 - 3192. [Abstract] [Full Text] [PDF] F. Hofmann The Biology of Cyclic GMP-dependent Protein Kinases J. Biol. Chem., January 7, 2005; 280(1): 1 - 4. [Full Text] [PDF] U. Walter and S. Gambaryan Roles of cGMP/cGMP-dependent protein kinase in platelet activation Blood, October 15, 2004; 104(8): 2609 - 2609. [Full Text] [PDF] A. Schafer, N. J. Alp, S. Cai, C. A. Lygate, S. Neubauer, M. Eigenthaler, J. Bauersachs, and K. M. Channon Reduced Vascular NO Bioavailability in Diabetes Increases Platelet Activation In Vivo Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1720 - 1726. [Abstract] [Full Text] [PDF] X. Du, J. A. Marjanovic, Z. Li, Y. Senis, S. Marshall, and S. Watson On the roles of cGMP and glycoprotein Ib in platelet activation Blood, June 1, 2004; 103(11): 4371 - 4372. [Full Text] [PDF] S. J. Marshall, Y. A. Senis, J. M. Auger, R. Feil, F. Hofmann, G. Salmon, J. T. Peterson, F. Burslem, and S. P. Watson GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase Blood, April 1, 2004; 103(7): 2601 - 2609. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020