title: Chaperone-like effects of cell-permeant ligands on opioid receptors.
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.
authors.affiliation: Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
mesh_terms: D002463:Cell Membrane Permeability; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008024:Ligands; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009292:Narcotic Antagonists; D017510:Protein Folding; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: D008024:Ligands; D018832:Molecular Chaperones; D009292:Narcotic Antagonists; D011957:Receptors, Opioid