Mechanisms and Modulation of Mu-Opioid Receptor Agonist Signaling

Abstract

AbstractThe mechanisms and signaling pathways by which acute and long-term administration of mu-opioid receptor agonists lead to a myriad of opioid effects are incompletely understood. The “life-cycle” of various signaling proteins and processes which may promote their “retirement” into a functionally inactive pool or their “re-utilization” could be important factors in attempts to modulate opioid signaling for optimal analgesia. G-protein-coupled receptors (GPCRs), G-pro-teins and G-protein subunit interactions, G-protein-coupled receptor kinases (GRKs), Dynamin II, G-protein-coupled receptor phosphatase (GRP), regulators of G-protein signaling (RGS), activators of G-protein signaling (AGS), s-arrestin, and phosducin-like proteins may contribute to modulating mu-opioid receptor agonist effects. It appears that different opioid agents may utilize different pathways or regulators and have different affinities for these various proteins. Furthermore, the same opioid agent may act differently in different en...