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J Vet Sci. 2018 Dec 4. [Epub ahead of print]

Characterization of distinct mechanism of agonist-induced canine platelet activation.

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Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.


Platelet activation plays a major role in hemostasis and thrombosis. Various agonists including ADP and thrombin interact with GPCRs which transduce signals from the cell surface to intracellular effectors through various G proteins. Recent studies have elucidated the role of these receptors and their corresponding G proteins in the regulation of events involved in platelet activation. However, these agonists-induced platelet activation in companion animals is poorly understood. This study was designed to characterize the platelet response to various agonists in dog platelets. We found that 2-methylthio-ADP (2-MeSADP)-induced dog platelet aggregation was blocked in the presence of either P2Y1 receptor antagonist MRS2179 or P2Y12 receptor antagonist AR-C69931MX, suggesting that co-activation of both the P2Y1 and the P2Y12 receptor is required for ADP-induced platelet aggregation. Thrombin-induced dog platelet aggregation was inhibited in the presence of either PKC inhibitor GF109203X or AR-C69931MX, suggesting that thrombin requires secreted ADP to induce platelet aggregation in dog platelets. In addition, thrombin-mediated Akt phosphorylation was inhibited in the presence of GF109203X or AR-C69931MX, indicating that thrombin causes Gi stimulation through P2Y12 receptor by secreted ADP in dog platelets. Unlike human and murine platelets, PAR4-activating peptide AYPGKF failed to cause dog platelet aggregation. Moreover, PAR1-activating peptide SFLLRN or co-stimulation of SFLLRN and AYPGKF failed to induce dog platelet aggregation. We conclude that ADP induces platelet aggregation through P2Y1 and P2Y12 receptors in dogs. Unlike human and murine platelets, selective activation of the PAR4 receptor may not be sufficient to cause platelet aggregation in dog platelets.


ADP; PAR4; dog; platelets; thrombin


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