Protein kinase C inhibitors enhance G-protein induced phospholipase A2 activation in intact human platelets

FEBS Letters
P IorioG Goracci

Abstract

Washed intact human platelets were prelabelled with [3H]arachidonic acid ([3H]AA) and stimulated with thrombin or with AlF4-, a known unspecific activator of G-proteins. Both stimuli induced the liberation of [3H]AA, the release of beta-thromboglobulin (beta-TG) and platelet aggregation. PMA did not induce liberation of [3H]AA although it induced beta-TG release and aggregation; preincubation with PMA did not modify significantly the amounts of [3H]AA and beta-TG released by thrombin or AlF4-. Different inhibitors of PKC (staurosporine, H-7 and calphostin C) increased the release of [3H]AA and inhibited beta-TG release and aggregation induced by AlF4- but they had no effect when platelets were stimulated with thrombin (0.5 U/ml). Calphostin C was able to release [3H]AA by itself without inducing aggregation of beta-TG release. Okadaic acid (a serine/threonine phosphoprotein phosphatase inhibitor) greatly inhibited the release of [3H]AA, beta-TG and aggregation in AlF4--stimulated platelets. These results indicate the presence of a G-protein mediated mechanism for the activation of a platelet phospholipase A2 which is negatively affected by a protein kinase, sensible to putative inhibitors of protein kinase C, and it is activate...Continue Reading

References

Jan 15, 1990·The Biochemical Journal·F RenduS Levy-Toledano
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Citations

Sep 21, 2002·Journal of Biochemical and Molecular Toxicology·María G Moya de JuriAna M Pechen de D'Angelo
Sep 6, 2000·Thrombosis Research·G I TognaL Caprino
Oct 23, 1997·Thrombosis Research·Y HashimotoK Nakahara
Jan 16, 1998·Prostaglandins, Leukotrienes, and Essential Fatty Acids·M Mutanen
Apr 15, 2011·The Journal of Biological Chemistry·Amanda J UnsworthCatherine J Pears
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·A S WeyrichG A Zimmerman
Mar 13, 1999·Biochemical Pharmacology·G Leoncini, M G Signorello

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