ArticleThe Journal of biological chemistry2009
Differential effect of membrane cholesterol removal on mu- and delta-opioid receptors: a parallel comparison of acute and chronic signaling to adenylyl cyclase.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Disruption of dopamine transmission by cholesterol depletion is associated with alterations in protein lipid raft partitioning and actin dynamics.Neuropharmacology · 2026Article
- Chemokine receptor activity is differentially regulated by membrane cholesterol.bioRxiv : the preprint server for biology · 2026Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.Nature communications · 2026Article
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Structural and dynamic studies uncover a distinct allosteric modulatory site at the μ-opioid receptor.bioRxiv : the preprint server for biology · 2025Article
- Confinement energy landscape classification reveals membrane receptor nano-organization mechanisms.Biophysical journal · 2024Article
- Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor.International journal of molecular sciences · 2023Review
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Docking cholesterol to integral membrane proteins with Rosetta.PLoS computational biology · 2023Article
- Patching holes in the mechanism of opioid tolerance.Trends in pharmacological sciences · 2023Article
- Opioid-Modulated Receptor Localization and Erk1/2 Phosphorylation in Cells Coexpressing μ-Opioid and Nociceptin Receptors.International journal of molecular sciences · 2023Article
- Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.Nature communications · 2022Article
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
- Allosteric Modulation of GPCRs of Class A by Cholesterol.International journal of molecular sciences · 2021Review
- Review
- Mouse TRPA1 function and membrane localization are modulated by direct interactions with cholesterol.eLife · 2019Article
- Allostery at opioid receptors: modulation with small molecule ligands.British journal of pharmacology · 2018Review
- Dynamic lateral organization of opioid receptors (kappa, muTraffic (Copenhagen, Denmark) · 2018Article
- Chronic opioid treatment augments caveolin-1 scaffolding: relevance to stimulatory μ-opioid receptor adenylyl cyclase signaling.Journal of neurochemistry · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
According to the lipid raft theory, the plasma membrane contains small domains enriched in cholesterol and sphingolipid, which may serve as platforms to organize membrane proteins. Using methyl-beta-cyclodextrin (MbetaCD) to deplete membrane cholesterol, many G protein-coupled receptors have been shown to depend on putative lipid rafts for proper signaling. Here we examine the hypothesis that treatment of HEK293 cells stably expressing FLAG-tagged mu-opioid receptors (HEK FLAG-mu) or delta-opioid receptors (HEK FLAG-delta) with MbetaCD will reduce opioid receptor signaling to adenylyl cyclase. The ability of the mu-opioid agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin to acutely inhibit adenylyl cyclase or to cause sensitization of adenylyl cyclase following chronic treatment was attenuated with MbetaCD. These effects were due to removal of cholesterol, because replenishment of cholesterol restored [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin responses back to control values, and were confirmed in SH-SY5Y cells endogenously expressing mu-opioid receptors. The effects of MbetaCD may be due to uncoupling of the mu receptor from G proteins but were not because of decreases in receptor number and were not mimicked by cytoskeleton disruption. In contrast to the results in HEK FLAG-mu cells, MbetaCD treatment of HEK FLAG-delta cells had no effect on acute inhibition or sensitization of adenylyl cyclase by delta-opioid agonists. The differential responses of mu- and delta-opioid agonists to cholesterol depletion suggest that mu-opioid receptors are more dependent on cholesterol for efficient signaling than delta receptors and can be partly explained by localization of mu- but not delta-opioid receptors in cholesterol- and caveolin-enriched membrane domains.
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What OpenQuestion holds
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.