Related Experiment Video

Updated: Oct 3, 2026

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
07:48

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis

Published on: July 3, 2015

Divers pathways mediate delta-opioid receptor down regulation within the same cell

M Shapira1, O Keren, M Gafni

  • 1The Mauerberger Chair in Neuropharmacology, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, 69978, Tel-Aviv, Israel.

Brain Research. Molecular Brain Research
|December 4, 2001
PubMed

Insights

Opioid receptor down regulation involves distinct mechanisms within the same cell, utilizing pathways like clathrin-coated pits and various kinases. Different cell types employ different kinase profiles for delta-opioid receptor regulation.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Neuroscience

Background:

  • Opioid receptor down regulation is crucial for understanding opioid tolerance and dependence.
  • Previous studies proposed various mechanisms for opioid receptor down regulation in different experimental systems.

Purpose of the Study:

  • To investigate if distinct mechanisms mediate opioid receptor down regulation within the same cell.
  • To elucidate the specific roles of different kinases and cellular pathways in delta-opioid receptor (DOR) down regulation.

Main Methods:

  • HEK-293 cells transfected with rat DOR were treated with etorphine and pharmacological agents.
  • Opioid receptor binding was measured using [(3)H]diprenorphine in isolated membranes and whole cells.
  • Internalization, degradation, and phosphorylation pathways were analyzed, including the roles of clathrin-coated pits, lysosomes, proteasomes, tyrosine kinase (TK), MAPK kinase (MEK), and G-protein-coupled receptor kinase (GRK).

Main Results:

  • Receptor internalization occurred via clathrin-coated pits, followed by degradation in lysosomes or proteasomes.
  • DOR down regulation in HEK-293 cells involved phosphorylation mediated by TK and MEK in parallel pathways, with a minor role for GRK.
  • In N18TG2 cells, GRK was the primary kinase for DOR down regulation, with minor roles for TK and MEK.

Conclusions:

  • Opioid receptor down regulation can occur through diverse pathways within a single cell.
  • Different cell types utilize distinct kinase profiles and receptor compartmentalization for mediating opioid receptor down regulation.

More Related Videos

Combining Laser Capture Microdissection and Microfluidic qPCR to Analyze Transcriptional Profiles of Single Cells: A Systems Biology Approach to Opioid Dependence09:54

Combining Laser Capture Microdissection and Microfluidic qPCR to Analyze Transcriptional Profiles of Single Cells: A Systems Biology Approach to Opioid Dependence

Published on: March 8, 2020

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method10:53

Preparation of Acute Brain Slices Using an Optimized N-Methyl-D-glucamine Protective Recovery Method

Published on: February 26, 2018

Related Concept Videos

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...
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...