Research Article| Volume 48, ISSUE 5, P379-384, May 1993

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The effects of genistein on platelet function are due to thromboxane receptor antagonism rather than inhibition of tyrosine kinase

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      Although several previous studies have indicated a role for tyrosine phosphorylated proteins in platelet function, their precise function and relationship to other biochemical processes remains elusive. In the present study genistein, an inhibitor of tyrosine kinase activity, was used to address this latter question. Genistein inhibited aggregation of washed human platelets in response to the thromboxane analogue U46619, to the phorbol ester phorbol myristate acetate, and to the calcium ionophore A23187. Only in the case of U46619, however, did the concentration of genistein required (IC50 of 10 μg/ml) correlate to that reported to inhibit tyrosine kinases. Likewise, genistein also inhibited U46619-induced serotonin secretion, elevation of cytosolic calcium, [32P]-phosphatidic acid production (an index of phospholipase C activity) and the phosphorylation of pleckstrin (an index of protein kinase C activity) at similar concentrations (IC50S of 4–9 μg/ml). U46619 caused the phosphorylation of a phosphoprotein which was insensitive to KOH digestion and therefore presumably a phosphotyrosine. This phosphorylation was also inhibited by genistein (IC50 of 6 μg/ml). However genistein also inhibited [3H]-U46619 binding to platelets with an IC50 of 3 μg/ml. These data suggest that the inhibitory effects of genistein on platelet activation occurs as a result of antagonism of the thromboxane receptor.
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      Further Reading

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        Direct activation of calcium activated, phospholipid dependent protein kinase by tumour promoting phorbol esters.
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        The role of protein kinase C in cell surface signal transduction and tumour promotion.
        Nature. 1984; 308: 693-698