Pharmacodynamic interplay of the P2Y₁, P2Y₁₂, and TxA₂ pathways in platelets: The potential of triple antiplatelet therapy with P2Y₁ receptor antagonism

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• 作者：Julie H. Oestreich^a ; ^{joestreich@unmc.edu} ; Suellen P. Ferraris^b ; Steven R. Steinhubl^c ; Wendell S. Akers^d
• 关键词：P2Y ; purinergic receptor subtype Y ; TxA2 ; thromboxane A2 ; LTA ; light transmittance aggregometry ; ADP ; adenosine diphosphate ; TRAP ; thrombin receptor activating peptide ; MFI ; mean fluorescence intensity
• 刊名：Thrombosis Research
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：131
• 期：2
• 页码：e64-e70
• 全文大小：499 K

文摘

Introduction

Previous work suggests that the extent of platelet inhibition by P2Y₁ receptor antagonism may be underappreciated, particularly in the context of dual antiplatelet therapy with aspirin and clopidogrel.

Materials and Methods

Using P2Y₁, P2Y₁₂, and TxA₂ receptor antagonists individually and in combination, we assessed the incremental changes from baseline platelet reactivity in blood collected from healthy volunteers.

Results

The P2Y₁ receptor antagonist further inhibited platelet activation and aggregation in several assay conditions ex vivo when combined with P2Y₁₂ and/or TxA₂ receptor blockers. Collagen and TRAP-induced platelet aggregation measured by light transmittance aggregometry was inhibited to a greater extent with the triple combination relative to each of the antagonists alone. The triple combination of P2Y₁, P2Y₁₂, and TxA₂ receptor antagonists also significantly shifted adenosine diphosphate (ADP)-stimulated platelet glycoprotein IIb/IIIa receptor and P-selectin expression compared to individual or dual antagonists.

Conclusions

These results substantiate that additional platelet inhibition occurs with the triple combination of P2Y₁, P2Y₁₂, and TxA₂ receptor antagonists and support further testing of P2Y₁ receptor antagonists as an option for alternative, synergistic, or triple antiplatelet therapy.