Early investigation of the endogenous targets of opioid drugs identified three main classes of opioid receptors: μ, δ, and κ. The cloning and characterization of the opioid receptors have impacted our understanding of their gene and protein structures. The MOPR is a member of the G-protein-coupled receptor (GPCR) family and interacts with (Gi/Go) heterotrimeric G-proteins. Activation of the receptor and subsequent dissociation of the G-proteins results in the opening of G-protein-gated inwardly-rectifying K+ (GIRK) channels, inhibition of voltage-gated Ca2+ channels, and reduction of adenylyl cyclase-mediated cAMP production, all of which serve to decrease membrane potential, neuronal excitability, and neurotransmitter release in addition to affecting second-messenger systems and gene expression.
