{"doi":"10.7554/elife.71689","title":"BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk","abstract":"Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide (GRP) and neuromedin B (NMB), respectively, to the spinal cord of mice. B-type natriuretic peptide (BNP) has been proposed to transmit both types of itch via its receptor NPRA encoded by Npr1 . However, BNP also binds to its cognate receptor, NPRC encoded by Npr3 with equal potency. Moreover, natriuretic peptides (NP) signal through the G i -couped inhibitory cGMP pathway that is supposed to inhibit neuronal activity, raising the question of how BNP may transmit itch information. Here, we report that Npr3 expression in laminae I-II of the dorsal horn partially overlaps with NMB receptor (NMBR) that transmits histaminergic itch via G q -couped PLCβ-Ca 2+ signaling pathway. Functional studies indicate that NPRC is required for itch evoked by histamine but not chloroquine (CQ), a nonhistaminergic pruritogen. Importantly, BNP significantly facilitates scratching behaviors mediated by NMB, but not GRP. Consistently, BNP evoked Ca 2+ responses in NMBR/NPRC HEK 293 cells and NMBR/NPRC dorsal horn neurons. These results reveal a previously unknown mechanism by which BNP facilitates NMB-encoded itch through a novel NPRC-NMBR cross-signaling in mice. Our studies uncover distinct modes of action for neuropeptides in transmission and modulation of itch in mice.","journal":"eLife","year":2021,"id":176921,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":273654,"name":"Xianyu Liu","orcid":"0000-0001-6089-8826","position":1,"is_corresponding":false},{"id":56826,"name":"Xueting Liu","orcid":"0000-0001-5419-198X","position":2,"is_corresponding":false},{"id":294779,"name":"Juan Liu","orcid":"0000-0003-3343-5521","position":3,"is_corresponding":false},{"id":273653,"name":"Admire Munanairi","orcid":"0000-0002-6698-3041","position":4,"is_corresponding":false},{"id":294775,"name":"Devin M. Barry","orcid":"0000-0002-3140-6121","position":5,"is_corresponding":false},{"id":294776,"name":"Benlong Liu","orcid":"0000-0002-9646-7531","position":6,"is_corresponding":false},{"id":720350,"name":"Hua Jin","orcid":"0000-0003-2662-2150","position":7,"is_corresponding":false},{"id":720351,"name":"Yu Sun","orcid":"0000-0001-9821-7862","position":8,"is_corresponding":false},{"id":294780,"name":"Qianyi Yang","orcid":"0000-0002-3353-1751","position":9,"is_corresponding":false},{"id":294777,"name":"Fang Gao","orcid":"0000-0003-0003-7818","position":10,"is_corresponding":false},{"id":720352,"name":"Li Wan","orcid":"0000-0002-8729-4018","position":11,"is_corresponding":false},{"id":721183,"name":"Jiahang Peng","orcid":null,"position":12,"is_corresponding":false},{"id":721184,"name":"Jinhua Jin","orcid":null,"position":13,"is_corresponding":false},{"id":720353,"name":"Kai‐Feng Shen","orcid":"0000-0002-8373-8275","position":14,"is_corresponding":false},{"id":161694,"name":"Ray Kim","orcid":null,"position":15,"is_corresponding":false},{"id":294782,"name":"Jun Yin","orcid":"0000-0001-7917-0608","position":16,"is_corresponding":false},{"id":294783,"name":"Ailin Tao","orcid":"0000-0002-0584-921X","position":17,"is_corresponding":false},{"id":296649,"name":"Zhou‐Feng Chen","orcid":null,"position":18,"is_corresponding":false},{"id":681938,"name":"Qingtao Meng","orcid":"0000-0002-1936-3050","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:47:28.018172Z","pmid":"34919054","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":[]}