Modulation of platelet function by extracellular adenosine triphosphate
G Soslau and J Parker
Department of Biological Chemistry, Hahnemann Medical School, Philadelphia,
PA 19102-1192.
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.
Volume 74,
Issue 3,
pp. 984-993,
08/15/1989
Copyright © 1989 by The American Society of Hematology
