| First Author | Psifogeorgou K | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 15 | Pages | 5617-24 |
| PubMed ID | 21490202 | Mgi Jnum | J:360373 |
| Mgi Id | MGI:7785715 | Doi | 10.1523/JNEUROSCI.4146-10.2011 |
| Citation | Psifogeorgou K, et al. (2011) A unique role of RGS9-2 in the striatum as a positive or negative regulator of opiate analgesia. J Neurosci 31(15):5617-24 |
| abstractText | The signaling molecule RGS9-2 is a potent modulator of G-protein-coupled receptor function in striatum. Our earlier work revealed a critical role for RGS9-2 in the actions of the mu-opioid receptor (MOR) agonist morphine. In this study, we demonstrate that RGS9-2 may act as a positive or negative modulator of MOR-mediated behavioral responses in mice depending on the agonist administered. Paralleling these findings we use coimmunoprecipitation assays to show that the signaling complexes formed between RGS9-2 and Galpha subunits in striatum are determined by the MOR agonist, and we identify RGS9-2 containing complexes associated with analgesic tolerance. In striatum, MOR activation promotes the formation of complexes between RGS9-2 and several Galpha subunits, but morphine uniquely promotes an association between RGS9-2 and Galphai3. In contrast, RGS9-2/Galphaq complexes assemble after acute application of several MOR agonists but not after morphine application. Repeated morphine administration leads to the formation of distinct complexes, which contain RGS9-2, Gbeta5, and Galphaq. Finally, we use simple pharmacological manipulations to disrupt RGS9-2 complexes formed during repeated MOR activation to delay the development of analgesic tolerance to morphine. Our data provide a better understanding of the brain-region-specific signaling events associated with opiate analgesia and tolerance and point to pharmacological approaches that can be readily tested for improving chronic analgesic responsiveness. |
