The role of ADP in endotoxin-induced equine platelet activation.
We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using a luminometric assay following incubation of heparinised equine whole blood with endotoxin (300 ng/ml). After addition of endotoxin ATP and ADP were released from the platelets and then subsequently degraded to AMP. WEB2086 (4-[3-[4-(o-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-s-triazolo[4,3-a][1, 4] diazepin-2-yl]proprionyl]-morpholine) (100 nM), a competitive PAF receptor antagonist, inhibited endotoxin-induced aggregation and also inhibited the release of adenine nucleotides from the platelets. It is concluded that endotoxin-induced aggregation is dependent upon ADP released from platelet dense granules.
Jarvis
G E
GE
Department of Clinical Veterinary Medicine, University of Cambridge, UK.
Evans
R J
RJ
Heath
M F
MF
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000502:physiology*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006736:Horses; D010972:Platelet Activating Factor / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013053:Spectrophotometry
D004731:Endotoxins; D010972:Platelet Activating Factor; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001081:Apyrase