The role of ADP in endotoxin-induced equine platelet activation

European Journal of Pharmacology
G E JarvisM F Heath

Abstract

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.

References

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Aug 1, 1963·The Journal of Physiology·G V BORN, M J CROSS

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Citations

Jan 25, 2003·Veterinary Immunology and Immunopathology·Cory C LalkoBenjamin J Darien
Apr 11, 2000·Research in Veterinary Science·S R BaileyF Cunningham
Dec 22, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Edward CedroneMarina A Dobrovolskaia
Nov 28, 2000·Equine Veterinary Journal·S R BaileyJ Elliott
Mar 6, 2004·The Journal of Biological Chemistry·Hisayo InbeJeffrey A Encinas

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