{"doi":"10.1111/bph.16145","title":"BQ788 reveals glial ET<sub>B</sub> receptor modulation of neuronal cholinergic and nitrergic pathways to inhibit intestinal motility: Linked to postoperative ileus","abstract":"Abstract Background and Purpose ET‐1 signalling modulates intestinal motility and inflammation, but the role of ET‐1/ET B receptor signalling is poorly understood. Enteric glia modulate normal motility and inflammation. We investigated whether glial ET B signalling regulates neural‐motor pathways of intestinal motility and inflammation. Experimental Approach We studied ET B signalling using: ET B drugs (ET‐1, SaTX, BQ788), activity‐dependent stimulation of neurons (high K + ‐depolarization, EFS), gliotoxins, Tg (Ednrb‐EGFP)EP59Gsat/Mmucd mice, cell‐specific mRNA in Sox10 CreERT2 ;Rpl22‐HAflx or ChAT Cre ;Rpl22‐HAflx mice, Sox10 CreERT2 ::GCaMP5g‐tdT, Wnt1 Cre2 ::GCaMP5g‐tdT mice, muscle tension recordings, fluid‐induced peristalsis, ET‐1 expression, qPCR, western blots, 3‐D LSM‐immunofluorescence co‐labelling studies in LMMP‐CM and a postoperative ileus (POI) model of intestinal inflammation. Key Results In the muscularis externa ET B receptor is expressed exclusively in glia. ET‐1 is expressed in RiboTag (ChAT)‐neurons, isolated ganglia and intra‐ganglionic varicose‐nerve fibres co‐labelled with peripherin or SP. ET‐1 release provides activity‐dependent glial ET B receptor modulation of Ca 2+ waves in neural evoked glial responses. BQ788 reveals amplification of glial and neuronal Ca 2+ responses and excitatory cholinergic contractions, sensitive to L‐NAME. Gliotoxins disrupt SaTX‐induced glial‐Ca 2+ waves and prevent BQ788 amplification of contractions. The ET B receptor is linked to inhibition of contractions and peristalsis. Inflammation causes glial ET B up‐regulation, SaTX‐hypersensitivity and glial amplification of ET B signalling. In vivo BQ788 (i.p., 1 mg·kg −1 ) attenuates intestinal inflammation in POI. Conclusion and Implications Enteric glial ET‐1/ET B signalling provides dual modulation of neural‐motor circuits to inhibit motility. It inhibits excitatory cholinergic and stimulates inhibitory nitrergic motor pathways. Amplification of glial ET B receptors is linked to muscularis externa inflammation and possibly pathogenic mechanisms of POI.","journal":"British Journal of Pharmacology","year":2023,"id":359381,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9651,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257223,"name":"Iveta Grants","orcid":null,"position":1,"is_corresponding":false},{"id":1110333,"name":"Egina C. Villalobos-Hernández","orcid":null,"position":2,"is_corresponding":false},{"id":1109986,"name":"Samhita Chaudhuri","orcid":"0000-0003-3845-0448","position":3,"is_corresponding":false},{"id":257221,"name":"Jonathon L. McClain","orcid":null,"position":4,"is_corresponding":false},{"id":892003,"name":"Luisa Seguella","orcid":"0000-0003-2346-9912","position":5,"is_corresponding":false},{"id":1109987,"name":"Derek M. Kendig","orcid":"0000-0002-3594-9916","position":6,"is_corresponding":false},{"id":1109988,"name":"Bryan A. Blakeney","orcid":"0000-0002-1509-8069","position":7,"is_corresponding":false},{"id":1110334,"name":"Srinivasa K. Murthy","orcid":null,"position":8,"is_corresponding":false},{"id":861783,"name":"Reiner Schneider","orcid":"0000-0002-7194-2703","position":9,"is_corresponding":false},{"id":861784,"name":"Patrick Leven","orcid":"0000-0002-6768-2523","position":10,"is_corresponding":false},{"id":618387,"name":"Sven Wehner","orcid":"0000-0002-8632-7631","position":11,"is_corresponding":false},{"id":1109989,"name":"Alan Harzman","orcid":"0000-0002-5450-4998","position":12,"is_corresponding":false},{"id":299690,"name":"John R. Grider","orcid":"0000-0002-0268-8772","position":13,"is_corresponding":false},{"id":255725,"name":"Brian D. Gulbransen","orcid":"0000-0003-1145-3227","position":14,"is_corresponding":false},{"id":1110335,"name":"Fedias L. Christofi","orcid":null,"position":15,"is_corresponding":false},{"id":862480,"name":"Elvio Mazzotta","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:13:52.889556Z","pmid":"37198101","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":[]}