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Cholesterol as a modulator of cannabinoid receptor CB 2 signaling.

التفاصيل البيبلوغرافية
العنوان: Cholesterol as a modulator of cannabinoid receptor CB 2 signaling.
المؤلفون: Yeliseev A; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA. yeliseeva@mail.nih.gov., Iyer MR; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA. malliga.iyer@nih.gov., Joseph TT; Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Coffey NJ; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA., Cinar R; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA., Zoubak L; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA., Kunos G; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA., Gawrisch K; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20852, USA.
المصدر: Scientific reports [Sci Rep] 2021 Feb 12; Vol. 11 (1), pp. 3706. Date of Electronic Publication: 2021 Feb 12.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Cholesterol/*metabolism , Receptor, Cannabinoid, CB2/*metabolism, Escherichia coli ; HEK293 Cells ; Humans ; Molecular Dynamics Simulation ; Receptor, Cannabinoid, CB2/isolation & purification
مستخلص: Signaling through integral membrane G protein-coupled receptors (GPCRs) is influenced by lipid composition of cell membranes. By using novel high affinity ligands of human cannabinoid receptor CB 2 , we demonstrate that cholesterol increases basal activation levels of the receptor and alters the pharmacological categorization of these ligands. Our results revealed that (2-(6-chloro-2-((2,2,3,3-tetramethylcyclopropane-1-carbonyl)imino)benzo[d]thiazol-3(2H)-yl)ethyl acetate ligand (MRI-2646) acts as a partial agonist of CB 2 in membranes devoid of cholesterol and as a neutral antagonist or a partial inverse agonist in cholesterol-containing membranes. The differential effects of a specific ligand on activation of CB 2 in different types of membranes may have implications for screening of drug candidates in a search of modulators of GPCR activity. MD simulation suggests that cholesterol exerts an allosteric effect on the intracellular regions of the receptor that interact with the G-protein complex thereby altering the recruitment of G protein.
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المشرفين على المادة: 0 (Receptor, Cannabinoid, CB2)
97C5T2UQ7J (Cholesterol)
تواريخ الأحداث: Date Created: 20210213 Date Completed: 20211213 Latest Revision: 20220823
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7881127
DOI: 10.1038/s41598-021-83245-6
PMID: 33580091
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-021-83245-6