Open Access
Chaperone-like effects of cell-permeant ligands on opioid receptors
Yong Chen1,Lee-Yuan Liu-Chen1
Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA
DOI: 10.2741/3269 Volume 14 Issue 2, pp.634-643
Published: 01 January 2009
(This article belongs to the Special Issue regulation and function of opioid receptor genes)

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.

Share and Cite
Yong Chen, Lee-Yuan Liu-Chen. Chaperone-like effects of cell-permeant ligands on opioid receptors. Frontiers in Bioscience-Landmark. 2009. 14(2); 634-643.