Translocation of arrestin induced by human A(3) adenosine receptor ligands in an engineered cell line: comparison with G protein-dependent pathways

Pharmacol Res. 2008 Apr;57(4):303-11. doi: 10.1016/j.phrs.2008.02.008. Epub 2008 Mar 8.


Structurally diverse ligands were studied in A(3) adenosine receptor (AR)-mediated beta-arrestin translocation in engineered CHO cells. The agonist potency and efficacy were similar, although not identical, to their G protein signaling. However, differences have also been found. MRS542, MRS1760, and other adenosine derivatives, A(3)AR antagonists in cyclic AMP assays, were partial agonists in beta-arrestin translocation, indicating possible biased agonism. The xanthine 7-riboside DBXRM, a full agonist, was only partially efficacious in beta-arrestin translocation. DBXRM was shown to induce a lesser extent of desensitization compared with IB-MECA. In kinetic studies, MRS3558, a potent and selective A(3)AR agonist, induced beta-arrestin translocation significantly faster than IB-MECA and Cl-IB-MECA. Non-nucleoside antagonists showed similar inhibitory potencies as previously reported. PTX pretreatment completely abolished ERK1/2 activation, but not arrestin translocation. Thus, lead candidates for biased agonists at the A(3)AR have been identified with this arrestin-translocation assay, which promises to be an effective tool for ligand screening.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenosine A3 Receptor Agonists
  • Animals
  • Arrestin / metabolism*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • GTP-Binding Proteins / physiology*
  • Protein Transport
  • Receptor, Adenosine A3 / physiology*
  • Signal Transduction / physiology*
  • Structure-Activity Relationship


  • Adenosine A3 Receptor Agonists
  • Arrestin
  • Receptor, Adenosine A3
  • Cyclic AMP
  • Extracellular Signal-Regulated MAP Kinases
  • GTP-Binding Proteins