Abstract
Defects in signal transduction mechanisms may underlie the impaired aggregation and secretion in patients with congenital platelet function defects (CPD). Both protein kinase C (PKC) induced pleckstrin phosphorylation and cytoplasmic Ca2+ mobilization play a major role in secretion. We postulated that combined platelet activation with a cell permeable direct PKC activator 1,2-dioctanoyl-sn-glycerol (DiC8) and ionophore A23187, which possibly bypass the steps involved in the intracellular synthesis of two major mediators (inositol trisphosphate, diacylglycerol), may induce normal dense granule secretion in patients with impaired receptor mediated secretion. We studied eight CPD patients with abnormal aggregation and secretion in response to several different surface receptor-mediated agonists despite the presence of normal dense granule contents. Receptor mediated Ca2+ mobilization and/or pleckstrin phosphorylation were abnormal in seven patients. Platelet activation with a combination of ADP (8 microM) with DiC8 (200 microM) or A23187 (10 microM) improved secretion in four patients. However, platelet activation with a combination of 200 microM DiC8 with 10 microM A23187, or 100 microM DiC8 with 5 microM A23187 induced normal se...Continue Reading
References
Apr 1, 1979·Prostaglandins and Medicine·R I LewyL Wiener
Jan 1, 1992·American Journal of Hematology·R RyoM Okuma
Jan 1, 1990·Annual Review of Physiology·T J Rink, S O Sage
Jun 1, 1989·Journal of Cellular Physiology·M H KrollA I Schafer
Nov 1, 1989·The Journal of Clinical Investigation·M MoroiK Shinmyozu
Dec 5, 1985·Nature·H K NieuwenhuisJ J Sixma
Jul 18, 1986·Science·Y Nishizuka
Jan 1, 1988·British Journal of Haematology·B Lages, H J Weiss
Apr 1, 1972·Analytical Biochemistry·H HolmsenH J Day
Apr 19, 1984·Nature·Y Nishizuka
Jun 1, 1981·The Journal of Clinical Investigation·K K WuY C Chen
Apr 1, 1995·The Journal of Clinical Investigation·P NurdenA Nurden
Sep 1, 1994·British Journal of Haematology·I J CartwrightF E Preston
Oct 1, 1994·The Journal of Clinical Investigation·T HirataS Narumiya
Jan 28, 1993·Nature·M J Berridge
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·J GabbetaA K Rao
Oct 4, 2003·Blood·Liansheng SunA Koneti Rao
Citations
Jan 22, 2004·Critical Reviews in Oncology/hematology·Indra Ramasamy
Mar 17, 2009·The Journal of Biological Chemistry·Yamini S BynagariSatya P Kunapuli
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·A K Rao
May 1, 2015·PloS One·Hari Priya VemanaFadi T Khasawneh
Feb 17, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·A K Rao, J Gabbeta
Oct 27, 2009·Platelets·Akeel BaigRichard J Haslam