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Molecular Pharmacology

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Research ArticleArticle

μ-Opioid Receptor Agonists Differentially Regulate the Expression of miR-190 and NeuroD

Hui Zheng, Yan Zeng, Xiaoxiao Zhang, Ji Chu, Horace H. Loh and Ping-Yee Law
Molecular Pharmacology January 2010, 77 (1) 102-109; DOI: https://doi.org/10.1124/mol.109.060848
Hui Zheng
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Yan Zeng
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Xiaoxiao Zhang
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Ji Chu
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Horace H. Loh
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Ping-Yee Law
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Abstract

The agonists of μ-opioid receptor (OPRM1) induce extracellular signal-regulated kinase (ERK) phosphorylation through different pathways: morphine uses the protein kinase C (PKC)-pathway, whereas fentanyl functions in a β-arrestin2-dependent manner. In addition, the two pathways result in the different cellular location of phosphorylated ERK and the activation of different sets of transcriptional factors. In the current study, the influence of the two pathways on the expression of microRNAs (miRNAs) was investigated. After treating the primary culture of rat hippocampal neurons and the mouse hippocampi with morphine or fentanyl for 3 days, seven miRNAs regulated by one or two of the agonists were identified. One of the identified miRNAs, miR-190, was down-regulated by fentanyl but not by morphine. This down-regulation was attenuated by 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126), which blocks the phosphorylation of ERK. When fentanyl-induced but not morphine-induced ERK phosphorylation was blocked in the primary cultures from β-arrestin2(−/−) mouse, fentanyl did not decrease the expression of miR-190. However, a PKC inhibitor that blocked morphine-induced ERK phosphorylation specifically had no effect on the miR-190 down-regulation. Therefore the decrease in miR-190 expression resulted from the agonist-selective ERK phosphorylation. In addition, the expressional changes in one of the miR-190 targets, neurogenic differentiation 1 (NeuroD), correlated with those in miR-190 expression, suggesting the OPRM1 could regulate the NeuroD pathways via the control of miR-190 expression.

Footnotes

  • This research was supported by the National Institutes of Health National Institute on Drug Abuse [Grants DA007339, DA016674, DA000564, DA011806, K05-DA70544, K05-DA00513].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.109.060848.

  • ABBREVIATIONS:

    GPCR
    G protein-coupled receptor
    ERK
    extracellular signal-regulated kinase
    PKC
    protein kinase C
    OPRM1
    μ-opioid receptor
    miRNA
    microRNA
    PCR
    polymerase chain reaction
    U0126
    1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene
    Ro-31-8425
    3-(8-(aminomethyl)-6,7,8,9-tetrahydropyrido(1,2-a)indol-10-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
    PP2
    4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine
    U73122
    1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione
    NeuroD
    neurogenic differentiation 1
    UTR
    untranslated region
    HEK
    human embryonic kidney
    CTOP
    Cys2-Tyr3-Orn5-Pen7-amide
    TIPPψ
    H-Tyr-Ticψ[CH2NH]-Phe-Phe-OH
    DMSO
    dimethyl sulfoxide
    PBS
    phosphate-buffered saline
    ANOVA
    analysis of variance
    %MPE
    percentage of maximum possible effect.

    • Received September 8, 2009.
    • Accepted October 23, 2009.
  • © 2010 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 77 (1)
Molecular Pharmacology
Vol. 77, Issue 1
1 Jan 2010
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Research ArticleArticle

μ-Opioid Receptor Agonists Differentially Regulate the Expression of miR-190 and NeuroD

Hui Zheng, Yan Zeng, Xiaoxiao Zhang, Ji Chu, Horace H. Loh and Ping-Yee Law
Molecular Pharmacology January 1, 2010, 77 (1) 102-109; DOI: https://doi.org/10.1124/mol.109.060848

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Research ArticleArticle

μ-Opioid Receptor Agonists Differentially Regulate the Expression of miR-190 and NeuroD

Hui Zheng, Yan Zeng, Xiaoxiao Zhang, Ji Chu, Horace H. Loh and Ping-Yee Law
Molecular Pharmacology January 1, 2010, 77 (1) 102-109; DOI: https://doi.org/10.1124/mol.109.060848
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