N-ethylmaleimide inhibition of thrombin-induced platelet aggregation.
The data presented in this report show that N-ethylmaleimide (NEM) is a powerful inhibitor of thrombin-induced platelet aggregation. NEM increased guanosine 3', 5'-cyclic monophosphate (cGMP) and adenosine 3', 5'-cyclic monophosphate (cAMP) levels in intact cells. The inhibition of cAMP high-affinity phosphodiesterase and cGMP phosphodiesterase was implicated in the elevation of the cyclic nucleotides. NEM dose dependently blocked the thrombin-stimulated, but not the phorbol myristate acetate-dependent phosphorylation of the protein kinase C substrate pleckstrin. Myosin light chain phosphorylation was also inhibited by NEM. In addition, the sulphydryl reagent inhibited Ca2+ mobilisation induced by thrombin. The data indicate that phospholipase C activation by thrombin is interrupted by NEM at the level of receptor-mediated signal transduction.
Leoncini
G
G
Istituto di Chimica Biologica, Università di Genova, Genoa, Italy. leoncini@unige.it
Signorello
M G
MG
D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology*; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D013439:Sulfhydryl Reagents; C039077:platelet protein P47; D000242:Cyclic AMP; D010738:Type C Phospholipases; D013917:Thrombin; D006152:Cyclic GMP; D005033:Ethylmaleimide; D002118:Calcium