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 c...

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Bibliographic Details
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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/S0014-2999(96)00637-1