The role of ADP in endotoxin-induced equine platelet activation

• Published in: European journal of pharmacology Vol. 315; no. 2; pp. 203 - 212
• Main Authors: Jarvis, Gavin E., Evans, Richard J., Heath, M.Fred
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14-11-1996; Elsevier
• Subjects: Adenine nucleotide; Adenosine Diphosphate - metabolism; Adenosine Diphosphate - physiology; Adenosine Monophosphate - metabolism; Adenosine Triphosphate - metabolism; Animals; Apyrase - pharmacology; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - metabolism; Endotoxin; Endotoxins - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Horses; Molecular and cellular biology; PAF (platelet-activating factor); Platelet; Platelet Activating Factor - physiology; Platelet Activation - drug effects; Platelet aggregation; Platelet Aggregation - drug effects; Spectrophotometry; PAF (platelet-activating factor); Platelet aggregation; Endotoxin; Adenine nucleotide; ADP; Platelet activating factor; Blood; Aggregation; Vertebrata; Platelet; Mammalia; Horse; Perissodactyla; Mechanism of action; Ungulata
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00637-1

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-6
H-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.