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Related Experiment Videos

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
Summary

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.

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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).

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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.