ArticleThe EMBO journal2002
Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 261 citations in OpenAlex.
- A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.The Journal of biological chemistry · 2012Trial
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Differential conservation analysis identifies residues defining constitutive internalization in beta-adrenergic receptors.iScience · 2026Article
- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
- Insights into cannabinoid receptor 2 (CB2) anterograde trafficking and pharmacological chaperoning.Cellular and molecular life sciences : CMLS · 2025Article
- Antagonists Enhance Cell-Surface Expression of Mammalian Odorant Receptors.International journal of molecular sciences · 2025Article
- Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.Nature communications · 2023Article
- Subcellular location defines GPCR signal transduction.Science advances · 2023Article
- Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin.Biomolecules · 2022Review
- Considerations on Using Antibodies for Studying the Dynorphins/Kappa Opioid Receptor System.Handbook of experimental pharmacology · 2022Article
- Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?Frontiers in molecular biosciences · 2022Review
- Dielectric Spectroscopy Based Detection of Specific and Nonspecific Cellular Mechanisms.Sensors (Basel, Switzerland) · 2021Article
- The Delta-Opioid Receptor; a Target for the Treatment of Pain.Frontiers in molecular neuroscience · 2020Review
- Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads.Frontiers in immunology · 2020Review
- Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.Proteins · 2019Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Dual RXR motifs regulate nerve growth factor-mediated intracellular retention of the delta opioid receptor.Molecular biology of the cell · 2019Article
- A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration.Nature communications · 2018Article
- Pharmacoperones as Novel Therapeutics for Diverse Protein Conformational Diseases.Physiological reviews · 2018Review
- Cognate Ligand Chaperoning: a Novel Mechanism for the Post-translational Regulation of Neurotransmitter Receptor Biogenesis.Frontiers in cellular neuroscience · 2017Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endoplasmic reticulum (ER) is recognized as an important site for regulating cell surface expression of membrane proteins. We recently reported that only a fraction of newly synthesized delta opioid receptors could leave the ER and reach the cell surface, the rest being degraded by proteasomes. Here, we demonstrate that membrane-permeable opioid ligands facilitate maturation and ER export of the receptor, thus acting as pharmacological chaperones. We propose that these ligands stabilize the newly synthesized receptor in the native or intermediate state of its folding pathway, possibly by inducing stabilizing conformational constrains within the hydrophobic core of the protein. The receptor precursors that are retained in the ER thus represent fully competent folding intermediates that can be targets for pharmacological intervention aimed at regulating receptor expression and cellular responsiveness. The pharmacological chaperone action is independent of the intrinsic signaling efficacy of the ligand, since both agonists and antagonists were found to promote receptor maturation. This novel property of G protein-coupled receptor ligands may have important implications when considering their effects on cellular responsiveness during therapeutic treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.