PMID- 31320243 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20200109 IS - 1347-8648 (Electronic) IS - 1347-8613 (Linking) VI - 140 IP - 2 DP - 2019 Jun TI - Possible biased analgesic of hydromorphone through the G protein-over beta-arrestin-mediated pathway: cAMP, CellKey, and receptor internalization analyses. PG - 171-177 LID - S1347-8613(19)34170-2 [pii] LID - 10.1016/j.jphs.2019.06.005 [doi] AB - Morphine, fentanyl, and oxycodone are widely used as analgesics, and recently hydromorphone has been approved in Japan. Although all of these are selective for mu-opioid receptors (MORs) and have similar structures, their analgesic potencies and adverse effects (AEs) are diverse. Recent molecular analyses of MOR signaling revealed that the G protein-mediated signaling pathway causes analgesic effects and the beta-arrestin-mediated signaling pathway is responsible for AEs. We used several cell-based analyses that selectively measure cellular responses activated by either G protein- or beta-arrestin-mediated pathways. GloSensor cAMP, CellKey, and receptor internalization assays were performed with four different types of cells stably expressing differentially labelled MOR. EC(50) values measured by cAMP and CellKey assays had potencies in the order fentanyl