Potential for modulation of platelet function via adenosine receptors during inflammation

Abstract

Traditionally, platelets are known to play an important role in haemostasis and thrombosis; however, they serve also as important modulators of inflammation and immunity. Platelets secrete adhesion molecules and cytokines, interact with leukocytes and endothelium, and express toll‐like receptors involved in a direct interaction with pathogens. Platelets express A2A and A2B subtypes of receptors for adenosine. The activation of these receptors leads to an increase in cAMP concentration in the cytoplasm, thereby resulting in inhibited secretion of pro‐inflammatory mediators and reduced cell activation. Therefore, platelet adenosine receptors could be a potential target for inhibiting platelet activation and thus down‐regulating inflammation or immunity. The biological effects of adenosine are short‐lasting, because the compound is rapidly metabolized; hence, its lability has triggered efforts to synthesize new, longer‐lasting adenosine analogues. In this article, we have reviewed the literature regarding the pharmacological potential of adenosine and other agonists of A2A and A2B receptors to affect platelet function during inflammation.

Pharmacology of Adenosine Receptors: Recent Advancements

“…Moreover, adenosine modulates B cell functions, with all four receptor subtypes being expressed [ 121 ]. Platelets express only A 2A and A 2B ARs, and when A 2A AR are activated, they inhibit the secretion of pro-inflammatory mediators, reduce cell activation, and decrease P-selectin expression [ 122 ]. New research highlights and corroborates the importance of AR modulation in the regulation of inflammation and in autoimmunity diseases.…”

Platelet purinergic receptors and non‐thrombotic diseases

“…This is complemented by a review of evidence for activation of P2Y 12 receptors in the dysregulated immune response during sepsis and the challenges associated with interpreting a dynamically changing inflammatory and then conversely immunosuppressed state, combined with activation of haemostatic pathways by Amoafo and colleagues (Amoafo et al, 2024). In another review, the potential role of adenosine is discussed (Boncler et al, 2024). Adenosine activation of platelet A 2A and A 2B receptors suppresses platelet activation during haemostasis.…”

“…Adenosine activation of platelet A 2A and A 2B receptors suppresses platelet activation during haemostasis. The potential control of platelet activation in the context of adenosine suppression of inflammation in thus introduced, including approaches to creating more stable analogues of adenosine (Boncler et al, 2024). Lastly, the discovery that activation of P2Y 12 receptors by various endogenous extracellular nucleotides can lead to selective platelet inflammatory functions and not aggregation (Arkless et al, 2024), leads to a discussion about the selective control of platelet activation by P2Y 1 receptors during inflammation compared to haemostasis, and the potential for safe anti-platelet drugs that suppress inflammation while preserving haemostasis (Pan et al, 2024).…”