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pubmed:abstractText |
An isoflavone compound, genistein, which is known as a protein tyrosine kinase inhibitor, concentration-dependently (0.1-30 micrograms/ml) suppressed human platelet aggregation, serotonin secretion, and protein tyrosine phosphorylation induced by collagen or stable thromboxane A2 analogs [U46619 and 9,11-epithio-11,12-methano-thromboxane A2 (STA2)]. However, genistein did not inhibit these thrombin (0.1 unit/ml)-induced platelet responses. Although thrombin induced an increase in the platelet phosphotyrosine content, genistein at 100 micrograms/ml only slightly attenuated thrombin-induced protein tyrosine phosphorylation. Genistein competitively inhibited [3H]U46619 binding to washed platelets, in a concentration-dependent fashion. Daidzein (another isoflavone compound), which does not have a hydroxyl group at the 5-position of genistein and lacks inhibitory activity for protein tyrosine kinase, was found to suppress [3H]U46619 binding, leading to the inhibition of collagen- or STA2-induced platelet responses. These results indicate that the blockage by genistein of platelet responses induced by collagen or thromboxane A2 is due to its preventive action on thromboxane A2 binding to the receptor, rather than via inhibition of protein tyrosine phosphorylation, and that the drug does not appear to be a particularly good inhibitor of tyrosine phosphorylation in intact platelets.
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