Signaling Properties of Structurally Diverse Kappa Opioid Receptor Ligands: Toward in Vitro Models of in Vivo Responses.
ACS chemical neuroscience August 21, 2019 Amelia D Dunn, Brian Reed, Jose Erazo et al.
A set of 21 structurally diverse kappa opioid receptor (KOR) ligands, including the natural product Salvinorin A and the endogenous peptide Dynorphin A(1-17), were tested in parallel to quantify biased signaling. Compounds were assessed for G-protein and β-arrestin recruitment in KOR-expressing U2OS cells, and a subset was tested for sedative properties in mice using the rotarod assay. Sedation significantly correlated with β-arrestin signaling, suggesting this in vitro system can predict this in vivo behavior. Downstream ERK1/2 and mTOR signaling diverged from G-protein and arrestin pathways.