{"doi":"10.1101/2022.05.18.492553","title":"ABHD6 selectively controls metabotropic-dependent increases in 2-AG production","abstract":"Abstract The most abundant endocannabinoid ( eCB ) in the brain, 2-arachidonoyl glycerol ( 2-AG) , is hydrolyzed by α/β-hydrolase domain containing 6 ( ABHD6 ); yet how ABHD6 controls stimuli-dependent increases in 2-AG production is unknown. To explore this question, we leveraged the recently developed 2-AG sensor, GRAB eCB2.0 , and found that stimulation of Neuro2a cells in culture with bradykinin ( BK ) acting at metabotropic B 2 K receptors and ATP acting at ionotropic P2X 7 receptors led to differential increases in 2-AG levels. B 2 K triggered increases in 2-AG levels via diacylglycerol lipase ( DAGL ), and this mechanism was potentiated by increases in intracellular calcium and ABHD6 inhibition. By contrast, P2X 7 -triggered increases in 2-AG levels were dependent on DAGL and extracellular calcium but unaffected by ABHD6 inhibition. Thus, ABHD6 preferentially regulates metabotropic-dependent increases in 2-AG levels over ionotropic-dependent increases in 2-AG levels. Our study indicates that ABHD6 selectively controls stimuli-dependent increases in 2-AG production and emphasizes its specific role in eCB signaling.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298258,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":987731,"name":"Dennis Sarroza","orcid":null,"position":1,"is_corresponding":false},{"id":987249,"name":"Anthony English","orcid":"0000-0003-4490-8654","position":2,"is_corresponding":false},{"id":517458,"name":"Dale Whittington","orcid":"0000-0002-6075-8812","position":3,"is_corresponding":false},{"id":571610,"name":"Ao Dong","orcid":"0000-0002-2821-9528","position":4,"is_corresponding":false},{"id":284799,"name":"Mario van der Stelt","orcid":"0000-0002-1029-5717","position":5,"is_corresponding":false},{"id":151125,"name":"Yulong Li","orcid":"0000-0002-9166-9919","position":6,"is_corresponding":false},{"id":262515,"name":"Larry S. Zweifel","orcid":"0000-0003-3465-5331","position":7,"is_corresponding":false},{"id":303878,"name":"Michael R. Bruchas","orcid":"0000-0003-4713-7816","position":8,"is_corresponding":false},{"id":370030,"name":"Benjamin B. Land","orcid":"0009-0007-4725-7929","position":9,"is_corresponding":false},{"id":507119,"name":"Nephi Stella","orcid":"0000-0002-4780-8360","position":10,"is_corresponding":false},{"id":987248,"name":"Simar Singh","orcid":"0000-0001-5785-8292","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"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":[]}