Differential opioid receptor expression and biochemical coupling profiles on glia
Salim F Kadhim1, John McDonald1, Mark F Bird1
1Department of Cardiovascular Sciences, Anaesthesia, Critical Care and Pain Management, University of Leicester, Hodgkin Building, Leicester LE1 9HN, UK.
Biochemical Pharmacology
|November 28, 2025
Summary
Opioid receptors (MOP, NOP) are expressed in astrocytes and oligodendrocytes, but not microglia, influencing cell function. Astrocytes can modulate microglial opioid receptor expression, impacting pain and immunomodulation.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- The opioid receptor family includes classical (MOP, KOP, DOP) and non-classical (NOP) receptors.
- The role and expression of opioid receptors in glial cells, crucial for pain processing and immunomodulation, remain controversial.
Purpose of the Study:
- To investigate the expression and function of opioid receptors (MOP, KOP, DOP, NOP) in various established and primary glial cell types.
- To determine if opioid receptor expression in microglia is influenced by astrocytes.
Main Methods:
- Utilized RT-PCR for mRNA expression analysis.
- Employed radioligand and fluorescent probe binding assays for receptor expression confirmation.
- Assessed receptor activation via MAPK pathway phosphorylation and cell migration using scratch assays.
Main Results:
- Mu-opioid receptor (MOP) mRNA was detected only in C6 and mouse primary astrocytes.
- Nociceptin/Orphanin FQ peptide receptor (NOP) mRNA was found in astrocytes and oligodendroglial cells (MO3.13, HOG).
- Microglia (EOC-20, primary) lacked opioid receptor mRNA unless exposed to astrocyte-conditioned media; MOP and NOP activation affected ERK1/2 phosphorylation and migration.
Conclusions:
- Opioid receptor expression is cell-type specific within glia, with astrocytes and oligodendrocytes expressing MOP and NOP.
- Astrocytes can modulate opioid receptor expression in microglia, suggesting a mechanism for astrocyte-glia communication in pain and immunomodulation.
- Further research is needed to elucidate the implications of astrocyte-modulated microglial opioid receptor expression in central nervous system functions.
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