Ligand Binding to Adenosine Receptors and the Inhibition of Adenylate Cyclase

It is now well established that many tissues contain specific extracellular adenosine receptors coupled to adenylate cyclase (Londos et al., 1983). Receptors mediating the inhibition of adenylate cyclase are classified as Ri or A1 receptors while those mediating the stimulation of adenylate cyclase are termed Ra or A2 receptors (Londos et al., 1983). While both R and R. receptors are blocked by methylxanthines, the structure activity relationships for agonists differ. N6 6substituted analogs such as N6-cyclohexyladenosine (CHA) and N6(L-phenylisopropyl)adenosine (L-PIA) are more potent than 5’-modified analogs such as 5’-N-ethylcarboxamide adenosine (NECA) in inhibiting adenylate cyclase activity while the opposite pertains for stimulating adenylate cyclase activity (Londos et al., 1983; Yeung and Green, 1984).