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

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Zhan-Guo Gao, Kenneth A Jacobson

Abstract

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.

Citations

May 6, 2011·Purinergic Signalling·Dennis Verzijl, Ad P Ijzerman
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Jul 1, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lauren T MayStephen J Hill
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Aug 13, 2015·Biochemical Pharmacology·Kenneth A Jacobson
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Sep 3, 2017·Molecular Pharmacology·Zhan-Guo Gao, Kenneth A Jacobson
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