title: μ-Opioid receptors and regulators of G protein signaling (RGS) proteins: from a symposium on new concepts in mu-opioid pharmacology.
abstract: Mu-opioid receptors (MOR) are the therapeutic target for opiate analgesic drugs and also mediate many of the side-effects and addiction liability of these compounds. MOR is a seven-transmembrane domain receptor that couples to intracellular signaling molecules by activating heterotrimeric G proteins. However, the receptor and G protein do not function in isolation but their activities are moderated by several accessory and scaffolding proteins. One important group of accessory proteins is the regulator of G protein signaling (RGS) protein family, a large family of more than thirty members which bind to the activated Gα subunit of the heterotrimeric G protein and serve to accelerate signal termination. This action negatively modulates receptor signaling and subsequent behavior. Several members of this family, in particular RGS4 and RGS9-2 have been demonstrated to influence MOR signaling and morphine-induced behaviors, including reward. Moreover, this interaction is not unidirectional since morphine has been demonstrated to modulate expression levels of RGS proteins, especially RGS4 and RGS9-2, in a tissue and time dependent manner. In this article, I will discuss our work on the regulation of MOR signaling by RGS protein activity in cultured cell systems in the context of other in vitro and behavioral studies. In addition I will consider implications of the bi-directional interaction between MOR receptor activation and RGS protein activity and whether RGS proteins might provide a suitable and novel target for medications to manage addictive behaviors.
authors: Department of Pharmacology and Substance Abuse Research Center, University of Michigan, Ann Arbor, MI 48109-5632, United States. jtraynor@umich.edu
authors: John
authors: J
authors: Traynor
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding; D020710:RGS Proteins / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D020710:RGS Proteins; D017450:Receptors, Opioid, mu