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.
Footnotes
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This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants DA00564, DA01583, DA11806, DA11190, K05-DA00153, K05-DA70554, K02-DA13926] and the F&A Stark Fund of the Minnesota Medical Foundation.
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ABBREVIATIONS: MOR, μ-opioid receptor; 3′-UTR, 3′-untranslated region; MOR1, major μ-opioid receptor transcript; RT-PCR, reverse transcription-polymerase chain reaction; qPCR, quantitative polymerase chain reaction; qRT-PCR, quantitative real-time polymerase chain reaction; HA, hemagglutinin; SBA, sodium butyric acid; miRNA, microRNA.
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The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.
- Received November 17, 2008.
- Accepted January 14, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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