title: GPCR screening via ERK 1/2: a novel platform for screening G protein-coupled receptors.
abstract: Discovery of novel agonists and antagonists for G protein-coupled receptors (GPCRs) relies heavily on cell-based assays because determination of functional consequences of receptor engagement is often desirable. Currently, there are several key parameters measured to achieve this, including mobilization of intracellular Ca2+ and formation of cyclic adenosine monophosphate or inositol triphosphate. However, no single assay platform is suitable for all situations, and all of the assays have limitations. The authors have developed a new high-throughput homogeneous assay platform for GPCR discovery as an alternative to current assays, which employs detection of phosphorylation of the key signaling molecule p42/44 MAP kinase (ERK 1/2). The authors show that ERK 1/2 is consistently activated in cells stimulated by Gq-coupled GPCRs and provides a new high-throughput platform for screening GPCR drug candidates. The activation of ERK 1/2 in Gq-coupled GPCR systems generates comparable pharmacological data for receptor agonist and antagonist data obtained by other GPCR activation measurement techniques.
authors.affiliation: TGR BioSciences Pty Ltd, 31 Dalgleish Street, Thebarton, SA 5031, Australia.
authors.forename: Ronald I W
authors.initials: RI
authors.lastname: Osmond
authors.forename: Antony
authors.initials: A
authors.lastname: Sheehan
authors.forename: Romana
authors.initials: R
authors.lastname: Borowicz
authors.forename: Emma
authors.initials: E
authors.lastname: Barnett
authors.forename: Georgina
authors.initials: G
authors.lastname: Harvey
authors.forename: Cheryl
authors.initials: C
authors.lastname: Turner
authors.forename: Andrea
authors.initials: A
authors.lastname: Brown
authors.forename: Michael F
authors.initials: MF
authors.lastname: Crouch
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Dyer
mesh_terms: D000818:Animals; D019556:COS Cells; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000032:analysis* / Q000037:antagonists & inhibitors; D014162:Transfection
chemical_list: D043562:Receptors, G-Protein-Coupled; D009496:Neurotensin; D002217:Carbachol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3