Recent improvements in the field of A₃ adenosine receptor ligands

Abstract

Adenosine regulates many physiological functions via specific cell membrane receptors. To date, four adenosine receptor subtypes have been cloned, A₁, A_2A, A_2B and A₃, each of which exhibits a unique tissue distribution, ligand affinity and signal transduction mechanism. The pathophysiological role of the A₃ receptor might be very different from that of the A₁ and A_2A subtypes, in that A₃ receptors could act as endogenous regulators under conditions of more severe challenge. To fully evaluate the biological role of these receptors, subtype-selective agonists and antagonists with high affinity are required. Although most of the available ligands are only moderately selective for human A₃ receptors, they have been useful probes to elucidate the function of this receptor subtype and have suggested a role for A₃ receptors in inflammation, neurodegeneration, asthma and cardiac ischaemia. Indeed, A₃ receptor antagonists have been hypothesised to act as potential anti-asthmatic, anti-inflammatory or cerebroprotective agents. Moreover, A₃ antagonists have been reported to induce apoptotic effects in some tumour cell lines at low concentration, whereas A₃ adenosine agonists appear to exert dual and opposite effects, either cytoprotective or cytotoxic, depending on the cell type and the level of receptor activation.

Keywords::

• A₃ receptor agonist
• A₃ receptor antagonist
• adenosine G protein
• therapeutic application