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Morphine-induced internalization of the L83I mutant of the rat μ-opioid receptor

A E Cooke1, S Oldfield, C Krasel

  • 1School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK.

British Journal of Pharmacology
|April 5, 2014
PubMed
Abstract

Insights

A MOP receptor variant (L83I) shows increased morphine-induced internalization, suggesting a ligand-selective biased receptor mechanism. This SNP may influence opioid tolerance and analgesic responses.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Neuroscience

Background:

  • Single-nucleotide polymorphisms (SNPs) in G-protein coupled receptors (GPCRs) can alter pharmacological properties.
  • Understanding micro-opioid receptor (MOP receptor) trafficking is crucial for opioid tolerance research.

Purpose of the Study:

  • To compare agonist-dependent trafficking and signaling of the MOP receptor L83I variant with the wild-type receptor.
  • To investigate the role of the L83I SNP in MOP receptor regulation.

Main Methods:

  • HEK 293 cells expressing wild-type or L83I MOP receptors were used.
  • Techniques included cell surface ELISA, confocal microscopy, immunoprecipitation, and functional signaling assays.

Main Results:

  • Morphine-induced internalization of the L83I MOP receptor was significantly increased compared to wild-type.
  • This enhanced internalization was specific to morphine and dependent on G-protein receptor kinase and dynamin.
  • Increased internalization was not linked to altered phosphorylation, arrestin association, or signaling ability.

Conclusions:

  • Morphine induces a specific conformation in the L83I variant, promoting internalization.
  • This represents a ligand-selective biased receptor, differing from the wild-type.
  • The L83I SNP may impact individual susceptibility to opioid tolerance and analgesia.
Keywords:
G-protein coupled receptormorphinereceptor internalizationμ-opioid receptor

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