@article {Wu744, author = {Qifang Wu and Lei Zhang and Ping-Yee Law and Li-Na Wei and Horace H. Loh}, title = {Long-Term Morphine Treatment Decreases the Association of μ-Opioid Receptor (MOR1) mRNA with Polysomes through miRNA23b}, volume = {75}, number = {4}, pages = {744--750}, year = {2009}, doi = {10.1124/mol.108.053462}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {μ-Opioid receptor (MOR) mediates most of the pharmacological effects of opioid drugs. The expression of MOR is temporarily and spatially regulated at both the transcriptional and post-transcriptional levels. Long-term morphine treatment that induces tolerance does not alter MOR mRNA expression, suggesting no direct link between agonist treatment and MOR gene transcription. We previously identified the 3'-untranslated region (3'-UTR) of the major transcript of μ-opioid receptor (MOR1) and revealed a novel trans-acting factor, miRNA23b, that binds to the K box motif in the 3'-UTR. The interaction between miRNA23b with the MOR1 3'-UTR suppressed receptor translation by inhibiting polysome-mRNA association. In this report, we demonstrate that long-term morphine treatment increases miRNA23b expression in a dose- and time-dependent manner and represses the association of MOR1 mRNA with polysomes through the MOR1 3'-UTR. The translational luciferase reporter assay shows a suppression effect of morphine on reporter activity that requires the MOR1 3'-UTR. This suggests a potential link between MOR expression and morphine treatment at the post-transcriptional level in which a specific miRNA, miRNA23b, is involved. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/75/4/744}, eprint = {https://molpharm.aspetjournals.org/content/75/4/744.full.pdf}, journal = {Molecular Pharmacology} }