title: Thrombin-induced human platelet aggregation is inhibited by protein-tyrosine kinase inhibitors, ST638 and genistein.
abstract: We have investigated the involvement of protein-tyrosine kinases in thrombin-induced aggregation of human platelets, using ST638 and genistein which are known inhibitors of protein-tyrosine kinase. Preincubation of platelets with 50 microM of ST638 or 25 micrograms/ml of genistein completely blocked the platelet aggregation induced with 0.05 unit/ml of thrombin. The increase of protein-tyrosine phosphorylation bands (135-, 124-, 76-, 64-, and 60-kDa) induced with thrombin was also inhibited by these inhibitors in a dose-dependent manner. These inhibitors also blocked the platelet aggregation and protein-tyrosine phosphorylation induced with thrombin in aspirin-treated platelets. Increase of the intracellular Ca2+ concentration induced by thrombin was also inhibited by higher concentrations of genistein. These results suggest that the protein-tyrosine phosphorylation plays a certain role in platelet activation having some relation to the intracellular Ca2+ concentration.
authors.affiliation: Department of Biochemistry, Fukui Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asahi
authors.forename: S
authors.initials: S
authors.lastname: Yanagi
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: T
authors.initials: T
authors.lastname: Inazu
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Yamamura
mesh_terms: D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002934:Cinnamates / Q000494:pharmacology*; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000097:blood / Q000302:isolation & purification; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013440:Sulfides / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D001798:Blood Proteins; D002934:Cinnamates; D007529:Isoflavones; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D013440:Sulfides; C060747:ST 638; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D013917:Thrombin; D002118:Calcium