FIGURE 1.

Biased signaling of Mu opioid receptors (MORs). The analgesic effects and adverse effects of MORs ligands are mediated by the G‐protein pathway and β‐arrestin pathway, respectively. The analgesic effects are mediated by G proteins, which inhibit AC, activate IRP channels, inhibit T‐type Ca²⁺ channels, and finally decrease the excitability of neurons. The adverse effects such as tolerance or respiratory depression are mediated by β‐arrestin 2, which leads to the internalization of the receptors. AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; Ca²⁺, calcium ion; Na⁺, sodion; IRP, inwardly rectifying potassium channels; GRKs, G‐protein receptor kinases; PKC, protein kinase C