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Morphine and fentanyl differently affect MOP and NOP gene expression in human neuroblastoma SH-SY5Y cells

Francesca Felicia Caputi1, Francesca Lattanzio, Donatella Carretta

  • 1Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.

Journal of Molecular Neuroscience : MN
|May 30, 2013
PubMed

Insights

Morphine decreases μ opioid receptor (MOP) and nociceptin/orphanin FQ-nociceptin receptor (NOP) gene expression, while fentanyl increases MOP expression. These distinct effects on opioid receptor gene expression offer insights into opioid tolerance mechanisms.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Opioid analgesics like morphine are vital for pain management but cause tolerance with long-term use.
  • Opioid tolerance involves complex cellular mechanisms, including changes in μ opioid receptor (MOP) and nociceptin/orphanin FQ-nociceptin receptor (NOP) systems.
  • Fentanyl, another potent opioid, exhibits different tolerance profiles compared to morphine.

Purpose of the Study:

  • To investigate the differential effects of morphine and fentanyl on MOP and NOP gene expression in human neuroblastoma SH-SY5Y cells.
  • To elucidate the role of MOP and NOP gene expression modulation in the development of opioid tolerance.

Main Methods:

  • SH-SY5Y cells were exposed to varying concentrations of morphine and fentanyl for different durations.
  • Quantitative real-time PCR was used to measure MOP and NOP mRNA levels.
  • The effect of naloxone pretreatment on gene expression was assessed.

Main Results:

  • Morphine (10 μM, 5h) significantly downregulated both MOP and NOP gene expression; this was reversed by naloxone.
  • Fentanyl (0.1 and 1 μM, 5-72h) significantly upregulated MOP gene expression, an effect also reversed by naloxone.
  • Fentanyl exposure did not alter NOP gene expression.

Conclusions:

  • Morphine and fentanyl exert distinct effects on MOP gene expression, contributing to understanding opioid tolerance.
  • Morphine influences NOP signaling, highlighting the nociceptin/orphanin FQ-nociceptin receptor system's role in morphine tolerance development.

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