P2Y₁ and P2Y₁₂ Receptors Mediate Aggregation of Dog and Cat Platelets: A Comparison to Human Platelets

Thrombosis is one of the most prevalent and serious health issues amongst humans. A key component of thrombotic events is the activation and aggregation of platelets, of which the P2Y₁ and P2Y₁₂ receptors play a crucial role in this process. Despite a breadth of knowledge on thrombosis and its mechanisms and treatment in various disorders in humans, there is less of an understanding of the expression and exact role of these receptors in companion animals such as dogs and cats. Therefore, this study aimed to investigate P2Y₁ and P2Y₁₂ receptors on dog and cat platelets in platelet-rich plasma and compare them to human platelets. Immunoblotting revealed the presence of P2Y₁ and P2Y₁₂ receptor proteins on dog and cat platelets, although relative amounts of each receptor appeared to contrast those of human platelets, with increased amounts of P2Y₁ compared to P2Y₁₂ receptors in dogs and cats. Using a modified 384-well plate aggregation assay, designed for use with small volumes, the human P2Y₁ and P2Y₁₂ receptor agonists adenosine 5'-diphosphate and 2-methylthio-adenosine 5'-diphosphate caused aggregation of dog and cat platelets. This aggregation was near-completely inhibited by the selective P2Y₁₂ antagonist ticagrelor. Aggregation of dog and cat platelets was partly inhibited by the human P2Y₁ receptor antagonist MRS2179. The agonist and antagonist responses in dog and cat platelets were like those of human platelets. In contrast, the aggregation of dog platelets in the absence of added nucleotides was two-fold greater than that of cats and humans. This study indicates that platelets of cats and dogs possess functional P2Y₁ and P2Y₁₂ receptors that can be inhibited by human antagonists. The data presented suggest differing roles or responses of the platelet P2Y receptors in dogs and cats compared to humans but also highlight the potential of using currently available P2Y₁ or P2Y₁₂ antiplatelet drugs such as ticagrelor for the treatment of thrombosis in these companion animals.