RT Journal Article
SR Electronic
T1 Long-Term Morphine Treatment Decreases the Association of μ-Opioid Receptor (MOR1) mRNA with Polysomes through miRNA23b
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 744
OP 750
DO 10.1124/mol.108.053462
VO 75
IS 4
A1 Qifang Wu
A1 Lei Zhang
A1 Ping-Yee Law
A1 Li-Na Wei
A1 Horace H. Loh
YR 2009
UL http://molpharm.aspetjournals.org/content/75/4/744.abstract
AB 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