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Opioid-Modulated Receptor Localization and Erk1/2 Phosphorylation in Cells Coexpressing μ-Opioid and Nociceptin

Guan-Yu Zhuo1, Ming-Chi Chen1, Tzu-Yu Lin2

  • 1Institute of Translational Medicine and New Drug Development, China Medical University, Taichung 40402, Taiwan.

International Journal of Molecular Sciences
|January 21, 2023
PubMed

Insights

Opioid drugs like morphine alter how μ-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors interact and move. Morphine enhances MOP-NOP receptor pairing and Erk1/2 phosphorylation, while buprenorphine primarily acts through NOP receptors.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • Opioid receptors, including μ-opioid (MOP) and nociceptin/orphanin FQ (NOP) receptors, play crucial roles in pain modulation and other physiological processes.
  • Understanding the complex interactions and signaling pathways of coexpressed opioid receptors is essential for developing targeted therapeutics.

Purpose of the Study:

  • To investigate the effects of opioids on the coexpression and heterodimerization of MOP and NOP receptors.
  • To examine opioid-induced alterations in receptor localization on lipid rafts and Erk1/2 phosphorylation.
  • To elucidate the distinct signaling mechanisms of morphine and buprenorphine through MOP and NOP receptors.

Main Methods:

  • Utilized two-photon microscopy and fluorescence resonance energy transfer (FRET) to assess MOP-NOP receptor proximity and heterodimerization.
  • Employed single-particle tracking (SPT) to analyze the movement of MOP-NOP heterodimers.
  • Conducted immunocytochemistry and immunoblotting to determine receptor localization on lipid rafts and Erk1/2 phosphorylation in HEK 293 cells.

Main Results:

  • Morphine, but not buprenorphine, facilitated MOP-NOP heterodimerization.
  • Both morphine and buprenorphine reduced the mobility of MOP-NOP heterodimers.
  • Morphine enhanced MOP-NOP colocalization on lipid rafts and stimulated Erk1/2 phosphorylation in cells expressing MOP or MOP+NOP receptors.
  • Buprenorphine selectively activated Erk1/2 phosphorylation through NOP receptors.

Conclusions:

  • Opioids can modulate the cellular localization and signaling of coexpressed MOP and NOP receptors.
  • Morphine and buprenorphine exhibit distinct mechanisms in regulating MOP-NOP receptor complex dynamics and downstream signaling.
  • These findings provide insights into the nuanced pharmacology of opioid receptor interactions and signaling pathways.
Keywords:
Erk1/2 (p44/p42 MAPK)fluorescence resonance energy transfer (FRET)lipid raftsnociceptin/orphanin FQ (NOP) receptorsingle-particle tracking (SPT)two-photon microscopyμ-opioid (MOP) receptor

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