Modulation of platelet function by extracellular adenosine triphosphate.
A potential physiologic role of extracellular adenosine triphosphate (ATP) on platelet function is proposed in this report. It is widely accepted that ATP competitively inhibits adenosine diphosphate (ADP)-induced platelet aggregation. Our observations of platelet aggregation with the agonists, collagen, epinephrine, and ADP in the presence of 180 mumol/L ATP could support this competitive nature of ATP. However, the disaggregation of maximally aggregated platelets induced by ATP, theophylline, or ATP plus theophylline indicates that additional mechanisms of ATP action may be present. Extracellular gamma-32P-ATP (7 pmol) labels surface-membrane proteins in intact platelets as demonstrated by several criteria. The reaction is Ca++-dependent. Stimulation by calcium occurs in the physiologic range of 1 to 5 mmol/L. Significant levels of phosphorylation occur within one minute with near maximal levels reached by five minutes. Platelet cyclic AMP (cAMP) levels were elevated in a dose-dependent fashion in cells incubated for four minutes with increasing amounts of extracellular ATP (18 to 540 nmol). The addition of ATP plus theophylline resulted in a synergistic stimulation of cAMP levels. ATP was not being hydrolyzed to adenosine by plasma nucleotidases, as demonstrated by the lack of effect of ten U of adenosine deaminase. The phosphorylation of surface proteins by extracellular ATP released from activated platelets may modulate platelet responsiveness to agonists at distances removed from the site of vascular injury. Phosphorylation may also play a role in signal transduction to regulate the levels of intracellular cAMP, which further inhibits platelet activation.
Soslau
G
G
Department of Biological Chemistry, Hahnemann Medical School, Philadelphia, PA 19102-1192.
Parker
J
J
D000255:Adenosine Triphosphate / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation; D012503:Saponins; D013347:Subcellular Fractions / Q000378:metabolism
D010750:Phosphoproteins; D012503:Saponins; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium