The role of receptor structure in determining adenosine receptor activity

Pharmacol Ther. 2000 Feb;85(2):55-75. doi: 10.1016/s0163-7258(99)00051-0.


Adenosine produces a wide variety of physiological effects through the activation of cell surface adenosine receptors (ARs). ARs are members of the G-protein-coupled receptor family, and currently, four subtypes, the A1AR, A2AAR, A2BAR, and A3AR, are recognized. This review focuses on the role of receptor structure in governing various facets of AR activity. Ligand-binding properties of ARs are primarily dictated by amino acids in the transmembrane domains of the receptors, although a role for extracellular domains of certain ARs has been suggested. Studies have identified certain amino acids conserved amongst AR subtypes that are critical for ligand recognition, as well as additional residues that may differentiate between agonist and antagonist ligands. Receptor regions responsible for activation of Gs have been identified for the A2AAR. The location of these intracellular sites is consistent with findings described for other G-protein-coupled receptors. Site-directed mutagenesis has been employed to analyze the structural basis for the differences in the kinetics of the desensitization response displayed by various AR subtypes. For the A2AAR and A3AR, agonist-stimulated phosphorylation of the AR, presumably via a G-protein receptor kinase, has been shown to occur. For these AR subtypes, intracellular regions or individual amino acids that may be targets for this phosphorylation have been identified. Finally, the role of A1AR gene structure in regulating the expression of this AR subtype is reviewed.

Publication types

  • Review

MeSH terms

  • Binding, Competitive
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Ligands
  • Receptors, Purinergic P1 / chemistry
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / physiology*
  • Signal Transduction


  • Ligands
  • Receptors, Purinergic P1
  • GTP-Binding Proteins