Abstract
We have investigated the effects of the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, on [3H]arachidonic acid release from human platelets. Both tyrosine kinase inhibitors blocked, in a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosine kinase inhibitors occurred early in the arachidonate release time course. Both genistein and methyl 2,5-dihydroxycinnamate also inhibited tyrosine phosphorylation in platelets. The inhibitors were specific in that they did not affect protein kinase C activity, ATP levels or mobilization of Ca2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A2 in platelets stimulated by the physiological ligands, thrombin and collagen.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / blood
-
Apyrase / pharmacology
-
Arachidonic Acid / metabolism*
-
Blood Platelets / drug effects*
-
Blood Platelets / metabolism
-
Calcium / blood
-
Cinnamates / pharmacology*
-
Collagen / pharmacology*
-
Enzyme Activation / drug effects
-
Genistein
-
Humans
-
Indomethacin / pharmacology
-
Isoflavones / pharmacology*
-
Phosphorylation
-
Protein Kinase C / metabolism
-
Protein Processing, Post-Translational / drug effects
-
Protein-Tyrosine Kinases / antagonists & inhibitors*
-
Signal Transduction / drug effects
-
Tetradecanoylphorbol Acetate / pharmacology
-
Thrombin / pharmacology*
Substances
-
Cinnamates
-
Isoflavones
-
Arachidonic Acid
-
daidzein
-
methyl 2,5-dihydroxycinnamate
-
Adenosine Triphosphate
-
Collagen
-
Genistein
-
Protein-Tyrosine Kinases
-
Protein Kinase C
-
Thrombin
-
Apyrase
-
Tetradecanoylphorbol Acetate
-
Calcium
-
Indomethacin