Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine

Prenus,Rose  V.; Luscar,Ebens; Zhu,Zhi-Ping; Badisa,Ramesh   B.; Goodman,Carl  B.

doi:10.3892/ijmm.2012.1132

Regulation of mammalian MOR-1 gene expression after chronic treatment with morphine

Authors:
- Rose V. Prenus
- Ebens Luscar
- Zhi-Ping Zhu
- Ramesh B. Badisa
- Carl B. Goodman
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Affiliations: College of Pharmacy and Pharmaceutical Sciences, Florida A__AMB__M University, Tallahassee, FL 32307, USA
Published online on: September 19, 2012 https://doi.org/10.3892/ijmm.2012.1132
Pages: 1493-1497

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Abstract

Morphine is an effective analgesic that acts by binding to the µ-opioid receptor (MOR) coded in the human by the OPRM1 gene. In the present study, we investigated the regulation of µ-opioid receptor (MOR-1) mRNA levels in all-trans-retinoic acid-differentiated SH-SY5Y human neuroblastoma cells under in vitro conditions with 10 µM morphine treatment for 24 h. In addition, we measured the MOR-1 levels in recombinant Chinese hamster ovary (CHO) cells, transfected with human µ-opioid receptor gene (hMOR) with 10 µM morphine treatment for 24 h. The isolated mRNA from these cells was subjected to real-time quantitative RT-PCR analysis to determine the regulation of µ-opioid receptor gene expression. It was observed that morphine treatment did not alter MOR-1 levels in undifferentiated SH-SY5Y cells compared to undifferentiated control cells. However, the MOR-1 levels in all-trans-retinoic acid-differentiated cells were significantly higher compared to the undifferentiated cells. Morphine treatment in differentiated SH-SY5Y cells caused significant downregulation of MOR-1 expression compared to the control cells. In the morphine-treated CHO cells, the hMOR-1 mRNA levels remained the same as the untreated control. Finally, pretreatment of SH-SY5Y cells with 10 µM naloxone, the antagonist of µ-opioid receptor, for 1 h significantly blocked the downregulation of MOR-1 mRNA levels with morphine treatment. These findings suggest that regulation of MOR-1 gene expression is cell-type specific after chronic morphine treatment and provide some evidence in the understanding of morphine tolerance.

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