Chaperone-like effects of cell-permeant ligands on opioid receptors

Front Biosci (Landmark Ed). 2009 Jan 1;14:634-43. doi: 10.2741/3269.

Abstract

The number of cell surface opioid receptors reflects a delicate balance between biosynthesis pathway and endocytosis pathway. The post-activation endocytic events such as internalization, recycling and degradation have been well-documented; however, only a few studies have been conducted on the regulatory events occurring along the protein biosynthesis pathway, including protein folding, endoplasmic reticulum (ER) export, ER-associated degradation, vesicular trafficking and membrane targeting and insertion. Accumulated in vitro evidence has demonstrated that expression of the opioid receptors, either wild-type or mutated, is subject to regulation by prolonged treatment with cell-permeant ligands that exert their regulatory effects post-transcriptionally. These hydrophobic ligands, both agonists and antagonists, were found to act in the ER like ER-resided molecular chaperones to positively affect stability, folding efficiency and/or ER export rate of newly-synthesized receptor proteins. Moreover, a number of observations demonstrated that long-term opioid antagonists up-regulated the receptors in vivo, in accord with the in vitro findings. Potential therapeutic applications of the chaperone-like function of opioid ligands are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Membrane Permeability
  • Endoplasmic Reticulum / metabolism
  • Ligands
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Narcotic Antagonists
  • Protein Folding
  • Receptors, Opioid / metabolism*

Substances

  • Ligands
  • Molecular Chaperones
  • Narcotic Antagonists
  • Receptors, Opioid