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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Shiraga, M. Articles by Matsuzawa, Y. Search for Related Content PubMed PubMed Citation Articles by Shiraga, M. Articles by Matsuzawa, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 10 (November 15), 1998: pp. 3710-3720 Involvement of Na+/Ca2+ Exchanger in Inside-Out Signaling Through the Platelet Integrin IIb3 Masamichi Shiraga, Yoshiaki Tomiyama, Shigenori Honda, Hidenori Suzuki, Satoru Kosugi, Seiji Tadokoro, Yuzuru Kanakura, Kenjiro Tanoue, Yoshiyuki Kurata, and Yuji Matsuzawa From the Second Department of Internal Medicine, Osaka University Medical School and Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan; and the Department of Cardiovascular Research, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. The platelet integrin IIb3 has become a new target for the treatment of pathological thrombosis. It becomes apparent that the affinity of IIb3 for its ligands is dynamically regulated by inside-out signaling. However, the components that couple diverse intracellular signals to the cytoplasmic domains of IIb3 remain obscure. Employing a chymotrypsin-induced IIb3 activation model, we previously proposed the hypothesis that Na+/Ca2 + exchanger (NCX) may be involved in inside-out signaling (Shiraga et al: Blood 88:2594, 1996). In the present study, employing two unrelated Na+/Ca2+ exchange inhibitors, 3,4-dichlorobenzamil (DCB) and bepridil, we investigated the role of NCX in platelet activation induced by various agonists in detail. Both inhibitors abolished platelet aggregation induced by all agonists examined via the inhibition of IIb3 activation. Moreover, these inhibitors abolished IIb3 activation induced by phorbol 12-myristate 13-acetate or A23187. On the other hand, neither of these inhibitors showed apparent inhibitory effects on protein phosphorylation of pleckstrin or myosin light chain, or an increase in intracellular calcium ion concentrations evoked by 0.1 U/mL thrombin. These effects of the NCX inhibitors are in striking contrast to those of protein kinase C inhibitor, Ro31-8220. Biochemical and ultrastructural analyses showed that NCX inhibitors, particularly DCB, made platelets "thrombasthenic". These findings suggest that the NCX is involved in the common steps of inside-out signaling through integrin IIb3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-H. Yi, P.-Y. Ho, T.-W. Chen, W.-J. Lin, V. Gukassyan, T.-H. Tsai, D.-W. Wang, T.-S. Lew, C.-Y. Tang, S. J. Lo, et al. Membrane Targeting and Coupling of NHE1-Integrin{alpha}IIb{beta}3-NCX1 by Lipid Rafts following Integrin-Ligand Interactions Trigger Ca2+ Oscillations J. Biol. Chem., February 6, 2009; 284(6): 3855 - 3864. [Abstract] [Full Text] [PDF] H. Kashiwagi, M. Shiraga, H. Kato, T. Kamae, N. Yamamoto, S. Tadokoro, Y. Kurata, Y. Tomiyama, and Y. Kanakura Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A Blood, August 1, 2005; 106(3): 913 - 921. [Abstract] [Full Text] [PDF]

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