{"doi":"10.7554/elife.52221","title":"β3-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes","abstract":"Cardiomyocyte β3-adrenoceptors (β3-ARs) coupled to soluble guanylyl cyclase (sGC)-dependent production of the second messenger 3’,5’-cyclic guanosine monophosphate (cGMP) have been shown to protect from heart failure. However, the exact localization of these receptors to fine membrane structures and subcellular compartmentation of β3-AR/cGMP signals underpinning this protection in health and disease remain elusive. Here, we used a Förster Resonance Energy Transfer (FRET)-based cGMP biosensor combined with scanning ion conductance microscopy (SICM) to show that functional β3-ARs are mostly confined to the T-tubules of healthy rat cardiomyocytes. Heart failure, induced via myocardial infarction, causes a decrease of the cGMP levels generated by these receptors and a change of subcellular cGMP compartmentation. Furthermore, attenuated cGMP signals led to impaired phosphodiesterase two dependent negative cGMP-to-cAMP cross-talk. In conclusion, topographic and functional reorganization of the β3-AR/cGMP signalosome happens in heart failure and should be considered when designing new therapies acting via this receptor.","journal":"eLife","year":2020,"id":94172,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9365,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469525,"name":"Peter Wright","orcid":"0000-0002-6504-590X","position":1,"is_corresponding":false},{"id":320720,"name":"Claire Poulet","orcid":"0000-0002-1063-5830","position":2,"is_corresponding":false},{"id":320721,"name":"Jose L. Sanchez‐Alonso","orcid":"0000-0003-2942-0079","position":3,"is_corresponding":false},{"id":397059,"name":"Catherine Mansfield","orcid":"0000-0002-5063-5181","position":4,"is_corresponding":false},{"id":469526,"name":"Andreas Friebe","orcid":"0000-0001-8178-3948","position":5,"is_corresponding":false},{"id":397062,"name":"Siân E. Harding","orcid":"0000-0002-3651-6354","position":6,"is_corresponding":false},{"id":242683,"name":"Jean‐Luc Balligand","orcid":"0000-0002-0522-4156","position":7,"is_corresponding":false},{"id":469527,"name":"Viacheslav O. Nikolaev","orcid":"0000-0002-7529-5179","position":8,"is_corresponding":false},{"id":320726,"name":"Julia Gorelik","orcid":"0000-0003-1148-9158","position":9,"is_corresponding":false},{"id":469524,"name":"Sophie Schobesberger","orcid":"0000-0001-8268-0019","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"32228862","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":[]}