ArticleBiochemical pharmacology2007
Cholesterol reduction by methyl-beta-cyclodextrin attenuates the delta opioid receptor-mediated signaling in neuronal cells but enhances it in non-neuronal cells.
Article in Biochemical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 86 citations in OpenAlex.
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?Pharmaceutics · 2022Review
- Isolation of Lipid Rafts by the Detergent-Based and Non-detergent-Based Methods for Localization of GPCRs with Immunoblotting and Laser Scanning Confocal Microscopy.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Post-translational Modifications of Opioid Receptors.Trends in neurosciences · 2020Review
- Location and Cell-Type-Specific Bias of Metabotropic Glutamate Receptor, mGluACS chemical neuroscience · 2019Article
- Is preoperative hypocholesterolemia a risk factor for severe postoperative pain? Analysis of 1,944 patients after laparoscopic colorectal cancer surgery.Journal of pain research · 2018Article
- Membrane cholesterol access into a G-protein-coupled receptor.Nature communications · 2017Article
- Article
- Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.Journal of bioenergetics and biomembranes · 2016Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
- Effects of Leucin-Enkephalins on Surface Characteristics and Morphology of Model Membranes Composed of Raft-Forming Lipids.The Journal of membrane biology · 2016Article
- Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.Lipids in health and disease · 2016Article
- Allosteric regulation of G protein-coupled receptor activity by phospholipids.Nature chemical biology · 2016Article
- Opioid receptors and cardioprotection - 'opioidergic conditioning' of the heart.British journal of pharmacology · 2015Review
- High Efficacy but Low Potency of δ-Opioid Receptor-G Protein Coupling in Brij-58-Treated, Low-Density Plasma Membrane Fragments.PloS one · 2015Article
- Lipid correlates of attentional impulsivity in first episode mania: results from an Indian population.Indian journal of psychological medicine · 2014Article
- Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection.American journal of physiology. Heart and circulatory physiology · 2014Article
- High- and low-affinity sites for sodium in δ-OR-Gi1α (Cys (351)-Ile (351)) fusion protein stably expressed in HEK293 cells; functional significance and correlation with biophysical state of plasma membrane.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.Frontiers in pharmacology · 2014Review
- The membrane protein LeuT in micellar systems: aggregation dynamics and detergent binding to the S2 site.Journal of the American Chemical Society · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Opioid receptors have been shown to be located in and regulated by lipid rafts/caveolae in caveolin-rich non-neuronal cells. Here, we found that caveolin-1 level was very low in rat brain and undetectable in NG108-15 cells, which endogenously express delta opioid receptors (DOR). Rat caudate putamen (CPu) membranes, NG108-15 cells and CHO cells stably transfected with FLAG-mouse-DOR (CHO-FLAG-mDOR) were homogenized, sonicated in a detergent-free 0.5M Na(2)CO(3) buffer and fractionated through discontinuous or continuous sucrose density gradients. About 70% of opioid receptors in CPu and DOR in both cell lines were present in low-density (5-20% sucrose) membrane domains enriched in cholesterol and ganglioside M1 (GM1), characteristics of lipid rafts in plasma membranes. In both cells, stimulation with permeable or non-permeable full agonists, but not with partial or inverse agonists, for 30min shifted approximately 25% of DORs out of rafts, by a naloxone-reversible and pertussis toxin-insensitive mechanism, which may undergo internalization. Methyl-beta-cyclodextrin (MCD) treatment greatly reduced cholesterol and shifted DOR to higher density fractions and decreased DPDPE affinities. MCD treatment attenuated DPDPE-induced [(35)S]GTPgammaS binding in CPu and NG108-15 cells, but enhanced it in CHO-FLAG-mDOR cells. In CHO-FLAG-mDOR cells, G(alphai) co-immunoprecipitated with caveolin-1, which was shown to inhibit G(alphai/o), and MCD treatment dramatically reduced the association leading to disinhibition. Thus, although localization in rafts and agonist-induced shift of DOR are independent of caveolin-1, lipid rafts sustain DOR-mediated signaling in caveolin-deficient neuronal cells, but appear to inhibit it in caveolin-enriched non-neuronal cells. Cholesterol-dependent association of caveolin-1 with and the resulting inhibition of G proteins may be a contributing factor.
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