Regulation of Opioid Receptor Trafficking and Morphine Tolerance by Receptor Oligomerization

@article{He2002RegulationOO,
  title={Regulation of Opioid Receptor Trafficking and Morphine Tolerance by Receptor Oligomerization},
  author={Li He and Jamie Fong and Mark Zastrow and Jennifer L. Whistler},
  journal={Cell},
  year={2002},
  volume={108},
  pages={271-282}
}
The utility of morphine for the treatment of chronic pain is hindered by the development of tolerance to the analgesic effects of the drug. Morphine is unique among opiates in its ability to activate the mu opioid receptor (MOR) without promoting its desensitization and endocytosis. Here we demonstrate that [D-Ala(2)-MePhe(4)-Gly(5)-ol] enkephalin (DAMGO) can facilitate the ability of morphine to stimulate MOR endocytosis. As a consequence, rats treated chronically with both drugs show reduced… 
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Opioid regulation of mu receptor internalisation: relevance to the development of tolerance and dependence.
TLDR
Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence.
Receptor trafficking induced by μ-opioid-receptor phosphorylation
TLDR
The current understandings of opioid-receptor phosphorylation, endocytosis and desensitization after repeated agonist treatments are reviewed and the role of G-protein coupled receptor kinases in opioid- receptorosphorylation is discussed.
Receptor Endocytosis Counteracts the Development of Opioid Tolerance
TLDR
It is demonstrated that the endocytotic potencies of opioid drugs are negatively correlated with their ability to cause receptor desensitization and opioid tolerance in HEK 293 cells, and shown that agonist-induced receptor endocytic facilitates the compensatory up-regulation of the cAMP pathway, a cellular hallmark of opioid withdrawal.
Regulated endocytosis of opioid receptors: cellular mechanisms and proposed roles in physiological adaptation to opiate drugs
TLDR
Certain mechanisms of opioid receptor desensitization and endocytosis are understood in considerable detail and the functional roles that these mechanisms play in the complex physiological adaptation of the intact nervous system to opiates are only beginning to be explored.
Morphine-Induced Receptor Endocytosis in a Novel Knockin Mouse Reduces Tolerance and Dependence
TLDR
The data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence.
Convallatoxin enhance the ligand-induced mu-opioid receptor endocytosis and attenuate morphine antinociceptive tolerance in mice
TLDR
Findings suggest convallatoxin are potentially therapeutic for morphine side effects and open a new avenue to study MOR trafficking.
Opioid receptor trafficking and interaction in nociceptors
TLDR
Analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy.
Role of delivery and trafficking of delta-opioid peptide receptors in opioid analgesia and tolerance.
TLDR
Experiments in animals show that MOP-receptor-mediated spinal analgesia is enhanced and morphine tolerance does not develop when DOP receptor functions are pharmacologically or genetically attenuated, indicating that the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance.
Agonist-induced regulation and trafficking of κ opioid receptors
TLDR
The bulk of the article describes the studies performed after cloning of the opioid receptors on regulation and trafficking of the κ opioid receptors (KORs) expressed in various cell systems.
Role of delivery and trafficking of δ-opioid peptide receptors in opioid analgesia and tolerance
TLDR
Experiments in animals show that MOP-receptor-mediated spinal analgesia is enhanced and morphine tolerance does not develop when DOP receptor functions are pharmacologically or genetically attenuated, indicating that the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance.
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