Adenosine receptors as drug targets

There are four adenosine receptors, A₁, A_2A, A_2B and A₃, together forming a defined subgroup of G protein coupled receptors. They are well conserved and widely expressed. The endogenous agonist, adenosine, has a minimal concentration in body fluids (20-200 nM) that is sufficient to slightly activate the receptors where they are very highly expressed—as in the basal ganglia, on fat cells and in the kidney. Here adenosine can play a physiological role and here antagonists such as caffeine can have effects in healthy individuals. Adenosine levels rise in stress and distress (up to 30 μM in ischemia) and tend to minimize the risk for adverse outcomes by increasing energy supply and decreasing cellular work, by stimulating angiogenesis, mediating preconditioning and having multiple effects on immune competent cells. These pathophysiological roles of adenosine also offer some potential drug targets, but the fact that adenosine receptors are involved in so many processes does not simplify drug development.