Abstract
Isolated human platelets represent a model system which could be used in in vitro cell toxicology for mechanistic studies on the short-term effects of cytotoxic compounds. We have recorded changes in the concentration of free cytosolic Ca2+ ([Ca2+]i) with Fura 2 in isolated human platelets treated with sphingosine, a compound suggested to be a specific inhibitor of protein kinase C (PKC). We huve shown that sphingosine is able to induce a rapid and transient release of Ca2+ from the intracellular stores in platelets. Furthermore, a massive efflux of released Ca2+ was shown. These effects of sphingosine on the human platelet might leave the cell incapable of performing Ca2+-dependent reactions, including PKC-mediated phosphorylation, upon stimulation subsequent to sphingosine-treatment.
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