title: Platelet-activating factor and not thromboxane A2 is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro.
abstract: Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The effects of quinacrine on platelet aggregation in citrated platelet-rich plasma induced by ADP and platelet-activating factor were also investigated. CV-3988 and WEB2086 caused a concentration-dependent inhibition of endotoxin-induced aggregation. The non-steroidal anti-inflammatories were without effect except flunixin meglumine which produced a small inhibition of endotoxin-induced aggregation. Quinacrine had a similar effect to the platelet-activating factor antagonists, but also non-competitively inhibited platelet aggregation in citrated platelet-rich plasma. It is concluded that platelet-activating factor is a critical mediator of endotoxin-induced platelet aggregation in the horse, but that products of cyclo-oxygenase metabolism are not of importance.
authors: Department of Clinical Veterinary Medicine, University of Cambridge, UK.
authors: G E
authors: GE
authors: Jarvis
authors: R J
authors: RJ
authors: Evans
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D006493:Heparin; D006736:Horses; D066298:In Vitro Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D002227:Carbazoles; D004731:Endotoxins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D013928:Thromboxane A2; C037913:CV 3988; C014558:flunixin meglumine; D006493:Heparin; D010741:Phospholipases A; D054467:Phospholipases A2; C007005:carprofen; D011796:Quinacrine; D001241:Aspirin; D003002:Clonixin