Figure 1

Opioid receptor signaling pathway. All four types of opioid receptor are coupled to the inhibitory G protein G_i or G_o, which in turn is regulated by RGS proteins. The analgesic effect of opioid agonists is attributed to the signal transduction through the G protein–mediated second messenger system initiated by the binding of an agonist to an opioid receptor. Once an opioid agonist binds to its specific receptor, the conformation of the opioid receptor changes, and the coupled G_i/o protein is subsequently activated. The G_α subunit switches from a GDP-bound inactive state to a GTP-bound active state and dissociates from the G_ßγ subunits. Activated G subunits then interact with downstream effectors, which further amplify the signal initiated by the opioid agonist and opioid receptor. Those downstream actions include the inhibition of adenylyl cyclase (AC) to reduce the production of cyclic AMP (cAMP), the opening of potassium channels, the inhibition of calcium channels, and the activation of mitogen-activated protein kinase (MAPK) and other kinases.