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In vivo visualization of delta opioid receptors upon physiological activation uncovers a distinct internalization

Lauren Faget1, Eric Erbs, Julie Le Merrer

  • 1Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67404 Illkirch, Cedex France.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|May 25, 2012
PubMed

Insights

Researchers visualized native G-protein-coupled receptors (GPCRs) in vivo, revealing distinct internalization patterns for physiological versus drug stimulation. This advance offers new ways to study GPCRs in living animals.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • G-protein-coupled receptors (GPCRs) are crucial for physiological functions and drug development.
  • Studying GPCR trafficking in vivo is challenging.
  • Understanding native receptor behavior is key to pharmacology.

Purpose of the Study:

  • To visualize and analyze the in vivo internalization of native delta opioid receptors (DORs) upon physiological stimulation.
  • To compare in vivo GPCR trafficking in response to physiological versus pharmacological stimuli.
  • To establish a novel in vivo visualization method for endogenous GPCRs.

Main Methods:

  • Generated knock-in mice with functional fluorescent DORs under endogenous promoter control.
  • Developed a context-dependent morphine withdrawal paradigm in mice.
  • Utilized in vivo imaging to track receptor internalization in the hippocampus (CA1 neurons).

Main Results:

  • Visualized transient, regionally restricted internalization of native DORs in CA1 neurons during context-dependent withdrawal.
  • Observed that a pool of surface receptors remained, contrasting with previous findings for exogenous drug-induced internalization.
  • Demonstrated distinct in vivo receptor trafficking responses to physiological versus pharmacological stimulation.

Conclusions:

  • Direct in vivo GPCR visualization is a powerful tool for studying endogenous receptor physiology.
  • Behavioral challenges can promote specific GPCR stimulation and trafficking patterns.
  • This approach enables mapping receptor activity promoted by endogenous systems and behavioral contexts.

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