Potential for modulation of platelet function via adenosine receptors during inflammation

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 A_2A and A_2B 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 A_2A and A_2B receptors to affect platelet function during inflammation. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.