Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy

Adenosine receptors are a subfamily of highly-conserved G-protein coupled receptors. They are found in the membranes of various human cells and play many physiological functions. Blood platelets express two (A_2A and A_2B) of the four known adenosine receptor subtypes (A₁, A_2A, A_2B, and A₃). Agonization of these receptors results in an enhanced intracellular cAMP and the inhibition of platelet activation and aggregation. Therefore, adenosine receptors A_2A and A_2B could be targets for anti-platelet therapy, especially under circumstances when classic therapy based on antagonizing the purinergic receptor P2Y₁₂ is insufficient or problematic. Apart from adenosine, there is a group of synthetic, selective, longer-lasting agonists of A_2A and A_2B receptors reported in the literature. This group includes agonists with good selectivity for A_2A or A_2B receptors, as well as non-selective compounds that activate more than one type of adenosine receptor. Chemically, most A_2A and A_2B adenosine receptor agonists are adenosine analogues, with either adenine or ribose substituted by single or multiple foreign substituents. However, a group of non-adenosine derivative agonists has also been described. This review aims to systematically describe known agonists of A_2A and A_2B receptors and review the available literature data on their effects on platelet function.