{"doi":"10.14814/phy2.15058","title":"β3 adrenergic receptor as potential therapeutic target in ADPKD","abstract":"Autosomal dominant polycystic kidney disease (ADPKD) disrupts renal parenchyma through progressive expansion of fluid-filled cysts. The only approved pharmacotherapy for ADKPD involves the blockade of the vasopressin type 2 receptor (V2R). V2R is a GPCR expressed by a subset of renal tubular cells and whose activation stimulates cyclic AMP (cAMP) accumulation, which is a major driver of cyst growth. The β3-adrenergic receptor (β3-AR) is a GPCR expressed in most segments of the murine nephron, where it modulates cAMP production. Since sympathetic nerve activity, which leads to activation of the β3-AR, is elevated in patients affected by ADPKD, we hypothesize that β3-AR might constitute a novel therapeutic target. We find that administration of the selective β3-AR antagonist SR59230A to an ADPKD mouse model (Pkd1fl/fl;Pax8rtTA;TetO-Cre) decreases cAMP levels, producing a significant reduction in kidney/body weight ratio and a partial improvement in kidney function. Furthermore, cystic mice show significantly higher β3-AR levels than healthy controls, suggesting a correlation between receptor expression and disease development. Finally, β3-AR is expressed in human renal tissue and localizes to cyst-lining epithelial cells in patients. Thus, β3-AR is a potentially interesting target for the development of new treatments for ADPKD.","journal":"Physiological Reports","year":2021,"id":188668,"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":16,"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":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":749889,"name":"Monica Carmosino","orcid":"0000-0001-7600-8816","position":1,"is_corresponding":false},{"id":750527,"name":"Samantha Chiurlia","orcid":null,"position":2,"is_corresponding":false},{"id":749890,"name":"Laura Onuchic","orcid":"0009-0008-4834-8651","position":3,"is_corresponding":false},{"id":749891,"name":"Mauro G. Mastropasqua","orcid":"0000-0002-8306-0839","position":4,"is_corresponding":false},{"id":749892,"name":"Eugenio Maiorano","orcid":"0000-0002-0472-5338","position":5,"is_corresponding":false},{"id":749893,"name":"Francesco Paolo Schena","orcid":"0000-0001-7927-5207","position":6,"is_corresponding":false},{"id":361706,"name":"Michael J. Caplan","orcid":"0000-0001-5768-4405","position":7,"is_corresponding":false},{"id":749888,"name":"Giorgia Schena","orcid":"0000-0001-5504-4834","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-18T23:49:10.350554Z","pmid":"34676684","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":[]}