Synergism between subthreshold concentrations of thrombin and 12-O-tetradecanoylphorbol 13-acetate in platelet activation.
A comparison was made between the time courses and interdependence of platelet aggregation, serotonin release, and cytosolic free Ca2+ concentration in the same sample of platelets loaded with [14C]-serotonin and Ca2+-sensitive photoprotein aequorin. In 100 micrograms/ml aspirin-treated platelets, neither 0.01 U/ml thrombin nor 50nM TPA, an active phorbol ester, induced significant aggregation, serotonin release, or a rise in the intracellular calcium concentration. However, when these two agents were added together, marked aggregation and release were observed without a change in the cytosolic free Ca2+ concentration. No correlation was observed between the extent of the synergistic effects and time of preincubation with TPA. Potentiatory effects of protein kinase C on receptor-mediated agonists need to be considered in platelet activation.
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Y
Y
Yatomi
M
M
Higashihara
A
A
Tanabe
T
T
Ohashi
H
H
Oka
S
S
Kume
D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D011493:Protein Kinase C / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*; D013917:Thrombin / Q000008:administration & dosage*
D012701:Serotonin; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium