Thromboxane A2 stimulates mitogen-activated protein kinase and arachidonic acid liberation in rabbit platelets.
U46619, a thromboxane A2 mimetic, caused tyrosine phosphorylation of several proteins in rabbit platelets. Among them, 42 kDa protein was identified as a mitogen-activated protein kinase (MAPK). U46619 activated MAPK in a concentration-dependent manner, measured by incorporation of 32P to a specific substrate for MAPK. U46619 also liberated [3H] arachidonic acid in a concentration-dependent manner. The U46619-induced MAPK activation and [3H]arachidonic acid liberation were inhibited by SQ29548 and by the removal of external Ca2+ ions. This is a first demonstration that TXA2 activates MAPK accompanied with arachidonic acid liberation in rabbit platelets.
Ohkubo
S
S
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University Aoba, Sendai, Japan.
Nakahata
N
N
Ohizumi
Y
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010761:Phosphorus Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D010766:Phosphorylation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010761:Phosphorus Radioisotopes; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium