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  • Title: Inhibition by the antilipogenic antibiotic cerulenin of thrombin-induced activation of human platelets.
    Author: Matsushima Y, Imai M, Ishimura Y, Ikeda Y, Nakata M, Kanegasaki S.
    Journal: Thromb Res; 1988 Jan 01; 49(1):79-90. PubMed ID: 3347929.
    Abstract:
    Upon incubation with an antibiotic cerulenin, human platelets lost their abilities to aggregate and to release serotonin or ATP in response to various stimuli such as thrombin, ADP, collagen and platelet activating factor. The loss of activities was dependent on both incubation time and cerulenin concentrations. As judged by 14C-serotonin release, concentrations of cerulenin required for the half-maximal inhibition of thrombin-induced activation were 5-10 and 70 micrograms/ml in the incubation for 120 min at 37 degrees C for washed platelets and those in platelet rich plasma, respectively. The cerulenin treatment also resulted in a significant inhibition of 14C-acetate incorporation into the lipid fraction of platelets, suggesting that de novo synthesis of fatty acids was inhibited by the treatment. No release of lactate dehydrogenase activity nor morphological changes in platelet structure was detected upon cerulenin treatment. When effects of cerulenin on intracellular Ca2+ concentration were examined, mobilization of intracellular Ca2+ by thrombin was significantly depressed in the cerulenin-treated platelets as judged by Fura2, Quin2 or chlortetracycline fluorescence. Since the influx of external Ca2+ is not essential to the thrombin-induced platelet activation (Rink, T. J. et al. FEBS Lett. 148 21-26, 1982), the results suggest that cerulenin-treatments affect the platelet function through the inhibition of intracellular Ca2+ mobilization.
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