Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Neurosci. 2012 May 23;32(21):7301-10. doi: 10.1523/JNEUROSCI.0185-12.2012.

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

Author information

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

Abstract

G-protein-coupled receptors (GPCRs) mediate numerous physiological functions and represent prime therapeutic targets. Receptor trafficking upon agonist stimulation is critical for GPCR function, but examining this process in vivo remains a true challenge. Using knock-in mice expressing functional fluorescent delta opioid receptors under the control of the endogenous promoter, we visualized in vivo internalization of this native GPCR upon physiological stimulation. We developed a paradigm in which animals were made dependent on morphine in a drug-paired context. When re-exposed to this context in a drug-free state, mice showed context-dependent withdrawal signs and activation of the hippocampus. Receptor internalization was transiently detected in a subset of CA1 neurons, uncovering regionally restricted opioid peptide release. Importantly, a pool of surface receptors always remained, which contrasts with the in vivo profile previously established for exogenous drug-induced internalization. Therefore, a distinct response is observed at the receptor level upon a physiological or pharmacological stimulation. Altogether, direct in vivo GPCR visualization enables mapping receptor stimulation promoted by a behavioral challenge and represents a powerful approach to study endogenous GPCR physiology.

PMID:
22623675
[PubMed - indexed for MEDLINE]
PMCID:
PMC3371401
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk