Stress Responsivity, Addiction, and a Functional Variant of the Human Mu-Opioid Receptor Gene

Intracellular signaling pathways of the μ-opioid receptor. Opioid receptors are coupled to inhibitory G_i/G_o heterotrimeric G proteins. Agonist binding to the receptor induces an exchange of GDP to GTP on the G protein which dissociates from the receptor; the alpha subunit also dissociates from the β/γ subunits. The GTP-bound α subunit inhibits the enzyme adenylyl cyclase (AC) leading to a decrease in intracellular cyclic AMP (cAMP) concentrations. The β/γ subunits activate G protein–activated inwardly rectifying potassium (GIRK) channels, and inhibit voltage-sensitive calcium channels. Each of these effector systems act to reduce neuronal excitability following agonist activation of the μ-opioid receptor. In vitro studies suggest that signal transduction through each of these pathways is altered by the A118G polymorphism of the μ-opioid receptor gene. Figure modified from (26). ©2001, used with permission from The American Physiological Association.