G Protein Coupled Receptor 139 (GPR139)

GPR139 is an orphan G-protein-coupled receptor (GPCR) that is expressed nearly exclusively in the central nervous system and may play a role in the control of locomotor activity. The signal transduction pathway and pharmacological function of GPR139, however, are still controversial due to the lack of natural or synthetic ligands. The authors report the characterization of human GPR139 signaling pathway and identification of surrogate agonists and antagonists.The authors screened a large library of small molecules for compounds that increase cAMP levels in GPR139-expressing cells and identified a compound with GPR139 agonist activity. This compound increased cAMP production specifically in cells expressing GPR139 but not in cells expressing its highly homologous receptor GPR142.