Platelet activation with combination of ionophore A23187 and a direct protein kinase C activator induces normal secretion in patients with impaired receptor mediated secretion and abnormal signal transduction

Thrombosis Research
X YangA K Rao

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

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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
Feb 17, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·A K Rao, J Gabbeta

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