The role of ADP in endotoxin-induced equine platelet activation.
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.
Publication Date: 1996-11-14 PubMed ID: 8960885DOI: 10.1016/s0014-2999(96)00637-1Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The article focuses on the impact of ADP (adenosine diphosphate) in causing platelet activation in horses when exposed to endotoxin, a toxic substance present in bacteria. The researchers concluded that this process is highly dependent on ADP released from certain cells within a horse’s blood platelets.
Role of ADP and ATP in Platelet Aggregation
- ADP and ATP, substances found in high concentrations within platelet dense granules, are known to activate platelets, causing them to aggregate, or clump together. Both these substances were the primary focus of the investigation in the context of endotoxin-induced platelet activation.
- The study reveals that ADP, when used through enzyme systems that scavenge it, can significantly reduce endotoxin-induced aggregation. This suggests that the presence of high amounts of ADP could potentially be responsible for the increased aggregation observed in the presence of endotoxins.
Impact of Endotoxins on ATP and ADP Levels
- Research was carried out by subjecting equine whole blood to endotoxin, in controlled conditions, to measure the changes in levels of ATP and ADP in plasma.
- The findings showed that the interaction with endotoxin led to the release of ATP and ADP from the platelets, and these substances were later degraded into AMP (adenosine monophosphate).
The Role of PAF Receptor Antagonist (WEB2086)
- The researchers also used WEB2086, an agent that competes with platelet activating factor (PAF) at the receptor level, to try and inhibit the action of endotoxins.
- The result showed that WEB2086 could not only inhibit aggregation but also prevented the release of adenine nucleotides (like ATP and ADP) from platelets in the presence of endotoxin.
Concluding Discoveries
- Basing on the results, the research concluded that endotoxin-induced aggregation in equine whole blood is highly dependent on the release of ADP from the platelet dense granules.
- This piece of knowledge could be immensely useful in understanding bacterial infections and could pave the way for future therapeutic strategies targeting ADP release or functionality in the context of equine bacterial infections or sepsis.
Cite This Article
APA
Jarvis GE, Evans RJ, Heath MF.
(1996).
The role of ADP in endotoxin-induced equine platelet activation.
Eur J Pharmacol, 315(2), 203-212.
https://doi.org/10.1016/s0014-2999(96)00637-1 Publication
Researcher Affiliations
- Department of Clinical Veterinary Medicine, University of Cambridge, UK.
MeSH Terms
- Adenosine Diphosphate / metabolism
- Adenosine Diphosphate / physiology
- Adenosine Monophosphate / metabolism
- Adenosine Triphosphate / metabolism
- Animals
- Apyrase / pharmacology
- Blood Platelets / metabolism
- Endotoxins / pharmacology
- Female
- Horses
- Platelet Activating Factor / physiology
- Platelet Activation / drug effects
- Platelet Aggregation / drug effects
- Spectrophotometry
Citations
This article has been cited 3 times.- Cedrone E, Neun BW, Rodriguez J, Vermilya A, Clogston JD, McNeil SE, Barenholz Y, Szebeni J, Dobrovolskaia MA. Anticoagulants Influence the Performance of In Vitro Assays Intended for Characterization of Nanotechnology-Based Formulations. Molecules 2017 Dec 21;23(1).
- Panther E, Dürk T, Ferrari D, Di Virgilio F, Grimm M, Sorichter S, Cicko S, Herouy Y, Norgauer J, Idzko M, Müller T. AMP affects intracellular Ca2+ signaling, migration, cytokine secretion and T cell priming capacity of dendritic cells. PLoS One 2012;7(5):e37560.
- Jarvis GE, Atkinson BT, Frampton J, Watson SP. Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb. Br J Pharmacol 2003 Feb;138(4):574-83.
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