Characterization of the distinct mechanism of agonist-induced canine platelet activation
Journal of Veterinary Science
; : 10-15, 2019.
Article
в En
| WPRIM
| ID: wpr-758889
Ответственная библиотека:
WPRO
ABSTRACT
Platelet activation has a major role in hemostasis and thrombosis. Various agonists including adenosine diphosphate (ADP) and thrombin interact with G protein-coupled receptors (GPCRs) which transduce signals through various G proteins. Recent studies have elucidated the role of GPCRs and their corresponding G proteins in the regulation of events involved in platelet activation. However, agonist-induced platelet activation in companion animals has not been elucidated. This study was designed to characterize the platelet response to various agonists in dog platelets. We found that 2-methylthio-ADP-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 P2Y₁₂ receptors is required for ADP-induced platelet aggregation. Thrombin-induced dog platelet aggregation was inhibited in the presence of either AR-C69931MX or the PKC inhibitor GF109203X, 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 the P2Y₁₂ receptor by secreted ADP in dog platelets. Unlike human and murine platelets, protease-activated receptor 4 (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 the P2Y₁ and P2Y₁₂ receptors in dogs. Unlike human and murine platelets, selective activation of the PAR4 receptor may be insufficient to cause platelet aggregation in dog platelets.
Key words
Полный текст:
1
База данных:
WPRIM
Основная тема:
Phosphorylation
/
Thrombosis
/
Blood Platelets
/
Thrombin
/
Platelet Activation
/
Adenosine Diphosphate
/
Platelet Aggregation
/
GTP-Binding Proteins
/
Receptors, Proteinase-Activated
/
Pets
Пределы темы:
Animals
/
Humans
Язык:
En
Журнал:
Journal of Veterinary Science
Год:
2019
Тип:
Article