{"doi":"10.1097/cd9.0000000000000076","title":"Effect of D4 Dopamine Receptor on Na+-K+-ATPase Activity in Renal Proximal Tubule Cells","abstract":"Objective: Dopamine, via its receptors, plays a vital role in the maintenance of blood pressure by modulating renal sodium transport. However, the role of the D 4 dopamine receptor (D 4 receptor) in renal proximal tubules (PRTs) is still unclear. This study aimed to verify the hypothesis that activation of D 4 receptor directly inhibits the activity of the Na + -K + -ATPase (NKA) in RPT cells. Methods: NKA activity, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were measured in RPT cells treated with the D 4 receptor agonist PD168077 and/or the D 4 receptor antagonist L745870, the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). Total D 4 receptor expression and its expression in the plasma membrane were investigated by immunoblotting in RPT cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Results: Activation of D 4 receptors with PD168077, inhibited NKA activity in RPT cells from WKY rats in a concentration- and time-dependent manner. The inhibitory effect of PD168077 on NKA activity was prevented by the addition of the D 4 receptor antagonist L745870, which by itself had no effect. The NO synthase inhibitor L-NAME and the soluble guanylyl cyclase inhibitor ODQ, which by themselves had no effect on NKA activity, eliminated the inhibitory effect of PD168077 on NKA activity. Activation of D 4 receptors also increased NO levels in the culture medium and cGMP levels in RPT cells. However, the inhibitory effect of D 4 receptors on NKA activity was absent in RPT cells from SHRs, which could be related to decreased plasma membrane expression of D 4 receptors in SHR RPT cells. Conclusions: Activation of D 4 receptors directly inhibits NKA activity via the NO/cGMP signaling pathway in RPT cells from WKY rats but not SHRs. Aberrant regulation of NKA activity in RPT cells may be involved in the pathogenesis of hypertension.","journal":"Cardiology Discovery","year":2022,"id":287176,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9661,"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":341617,"name":"Hongmei Ren","orcid":"0000-0003-0210-1502","position":1,"is_corresponding":false},{"id":341619,"name":"Hongyong Wang","orcid":"0000-0002-3673-9283","position":2,"is_corresponding":false},{"id":332117,"name":"Pedro A. José","orcid":"0000-0003-1507-7556","position":3,"is_corresponding":false},{"id":332120,"name":"Chunyu Zeng","orcid":"0000-0003-0173-5028","position":4,"is_corresponding":false},{"id":672280,"name":"Tianyang Xia","orcid":"0000-0003-3363-036X","position":5,"is_corresponding":false},{"id":372075,"name":"Jian Yang","orcid":"0000-0003-2954-758X","position":6,"is_corresponding":false},{"id":343158,"name":"Duofen He","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:29:56.781756Z","pmid":"36969984","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":[]}