Mechanisms involved in adenosine triphosphate--induced platelet aggregation in whole blood.
OBJECTIVE
Effects on platelet aggregation of adenosine triphosphate (ATP) released from damaged cells and from platelets undergoing exocytosis have not been clearly established. In this study we report on the effects of ATP on platelet aggregation in whole blood.


RESULTS
Aggregation, measured using a platelet-counting technique, occurred in response to ATP and was maximal at 10 to 100 micromol/L. It was abolished by MRS2179, AR-C69931, and creatine phosphate/creatine phosphokinase, implying that conversion to adenosine diphosphate (ADP) is required. ATP did not induce aggregation in platelet-rich plasma, but aggregation did occur when apyrase or hexokinase was added. Aggregation also occurred after addition of leukocytes to platelet-rich plasma (as a source of ecto-ATPase), and this was potentiated on removal of adenosine by adenosine deaminase, indicating that adenosine production modulates the response. Dipyridamole, which inhibits adenosine uptake into erythrocytes, inhibited aggregation induced by ATP in whole blood, and adenosine deaminase reversed this. DN9693 and forskolin synergized with dipyridamole to inhibit ATP-induced aggregation.


CONCLUSIONS
ATP induces aggregation in whole blood via conversion of ATP to ADP by ecto-ATPases on leukocytes. This is inhibited by agents that prevent adenosine removal. Reduced aggregation at high concentrations of ATP (>100 micromol/L) may be a consequence of inhibition by ATP of ADP action at ADP receptors.
Stafford
Nicholas P
NP
Centre for Integrated Systems Biology and Medicine, University of Nottingham, UK.
Pink
Andrew E
AE
White
Ann E
AE
Glenn
Jacqueline R
JR
Heptinstall
Stan
S
D000243:Adenosine Deaminase / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000925:Anticoagulants; D004176:Dipyridamole / Q000494:pharmacology; D006629:Hirudins; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D010949:Plasma / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*
D000925:Anticoagulants; D006629:Hirudins; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase