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Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...

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Localization and regulation of fluorescently labeled delta opioid receptor, expressed in enteric neurons of mice.

Daniel P Poole1,2, Juan-Carlos Pelayo1, Gregory Scherrer3

  • 1Department of Surgery, University of California, San Francisco.

Gastroenterology
|June 25, 2011
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The delta opioid receptor (DOR) is found in specific gut neurons, explaining how DOR agonists affect gut function. Activation leads to receptor removal and slow replenishment, potentially causing tolerance to these drugs.

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Area of Science:

  • Gastroenterology
  • Neuroscience
  • Pharmacology

Background:

  • Opioids and opiates impact gastrointestinal functions through μ, δ, and κ receptors.
  • Delta opioid receptor (DOR) agonists suppress gut motility and secretion.
  • The precise localization and regulation of DOR in the gastrointestinal tract remain largely uncharacterized.

Purpose of the Study:

  • To investigate the localization of DOR within the gastrointestinal tract.
  • To determine how DOR agonists regulate the subcellular distribution of DOR.
  • To elucidate the role of DOR in regulating gastrointestinal functions.

Main Methods:

  • Utilized genetically engineered mice expressing enhanced green fluorescent protein (eGFP) inserted into the Oprd1 gene (encoding DOR) to create DOReGFP.
  • Examined the expression and localization of DOReGFP in various regions of the mouse gastrointestinal tract.
  • Investigated the regulation of DOReGFP subcellular distribution in response to agonist stimulation.

Main Results:

  • DOReGFP was expressed in enteric neurons and fibers within the muscularis externa across all gastrointestinal regions.
  • In the small intestine, DOReGFP was found in submucosal secretomotor/vasodilator neurons and myenteric excitatory/inhibitory neurons.
  • DOReGFP was primarily in nitrergic myenteric neurons of the colon, often co-expressed with μ opioid receptors, and its trafficking involved endocytosis and slow replenishment via de novo synthesis.

Conclusions:

  • DOR specifically localizes to submucosal and myenteric neurons, providing a basis for its inhibitory effects on gastrointestinal secretion and motility.
  • Agonist-induced sustained down-regulation of DOR at the plasma membrane may lead to long-lasting tolerance to DOR agonists.
  • Understanding DOR localization and regulation is crucial for developing targeted therapies for gastrointestinal disorders.