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 (A(1), A(2A), A(2B), and A(3)). 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 P2Y(12) 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.