{"doi":"10.1038/s41598-021-83245-6","title":"Cholesterol as a modulator of cannabinoid receptor CB2 signaling","abstract":"Abstract 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(2 H )-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.","journal":"Scientific Reports","year":2021,"id":169058,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260244,"name":"Malliga R. Iyer","orcid":"0000-0002-0116-4619","position":1,"is_corresponding":false},{"id":423531,"name":"Thomas T. Joseph","orcid":"0000-0003-1323-3244","position":2,"is_corresponding":false},{"id":630280,"name":"Nathan J. Coffey","orcid":"0000-0002-9413-5533","position":3,"is_corresponding":false},{"id":260243,"name":"Reşat Çınar","orcid":"0000-0002-8597-7253","position":4,"is_corresponding":false},{"id":379907,"name":"Lioudmila Zoubak","orcid":null,"position":5,"is_corresponding":false},{"id":243202,"name":"George Kunos","orcid":"0000-0003-1788-4976","position":6,"is_corresponding":false},{"id":378872,"name":"Klaus Gawrisch","orcid":"0000-0002-0841-1539","position":7,"is_corresponding":false},{"id":378871,"name":"Alexei Yeliseev","orcid":"0000-0003-4131-0913","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:46:11.334362Z","pmid":"33580091","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}