Elevation of cAMP in human platelets inhibits thrombin- but not collagen-induced tyrosine phosphorylation.
Both thrombin and collagen induced the phosphorylation of tyrosine in numerous proteins in platelets, with collagen causing the phosphorylation of an additional 40 kDa protein. Thrombin-induced phosphorylation was markedly inhibited when cAMP was elevated with iloprost. Iloprost or the combination of iloprost, inhibitors of positive feedback and cytochalasin D also partially inhibited collagen-induced phosphorylation. By contrast, iloprost had no effect on phosphorylation induced by collagen in the presence of inhibitors of positive feedback by released ADP, TxA2 and fibrinogen and in platelets containing BAPTA to prevent increases in cytosolic Ca2+. The results indicate that collagen-induced tyrosine phosphorylation may be a fundamental pathway in hemostasis which can function even when platelet cAMP is elevated.
Smith
J B
JB
Department of Pharmacology, Temple University Medical School, Philadelphia, Pa 19140.
Dangelmaier
C
C
Daniel
J L
JL
D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology*; D003402:Creatine Kinase / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010725:Phosphocreatine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism*
D009842:Oligopeptides; D010725:Phosphocreatine; D015638:Cytochalasin D; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D000242:Cyclic AMP; D003402:Creatine Kinase; D013917:Thrombin; D016285:Iloprost