Comparison of two downstream signaling pathways in the µ-opioid receptors activated by several opioids

In Japan, morphine (MRP), fentanyl (FEN), oxycodone (OXY) and hydromorphone (HDM) have been approved as pain analgesics in palliative and supportive care. Although all of them are selective for µ-opioid receptors (µOR), their receptor-activated signaling properties are different. Moreover, the combined and switching effets among them are complicated. Recent molecular analyses of the properties of µOR revealed two downstream pathways either eliciting analgesic effects through a G protein-mediated pathway or through the β-arrestin-mediated pathway that causes adverse events (AEs). However, molecular charactrerization of interaction among opioids has not investigated sufficiently. We therefore investigated characterization of these opioids using cells stably expressing µOR by three cell-based CellKeyTM, GloSensorTM cAMP and internalization assays.