{"doi":"10.17615/ejt5-kk26","title":"The Natriuretic Peptide Uroguanylin Elicits Physiologic Actions Through 2 Distinct Topoisomers","abstract":"The peptide uroguanylin regulates electrolyte transport in the intestine and kidney. Human uroguanylin has two conformations that can be stably isolated, owing to their slow interconversion rate. The A isomer potently activates the guanylate cyclase-C receptor found primarily in the intestine. The B isomer, by contrast, is a very weak agonist of this receptor, leading to a widely-held assumption that it is physiologically irrelevant. We show here, however, that human uroguanylin B has potent natriuretic activity in the kidney. Interestingly, uroguanylin A and B both induce saliuretic responses, but the activity profiles for the two peptides differ markedly. The uroguanylin B dose-response curve is sigmoidal with a threshold dose near 10 nmol/kg body weight, whereas uroguanylin A has a comparable threshold, but a bell-shaped dose-response curve. Additionally, our study indicates a unique interplay between the A and B isoforms, such that the A form at high concentrations antagonizes the natriuretic action of the B form. These data show that the kidney contains a uroguanylin receptor whose pharmacological profile does not match that of the well-defined intestinal uroguanylin receptor (guanylate cyclase-C), an observation consistent with previous studies showing that the kidney of the guanylate cyclase-C knockout mouse remains responsive to uroguanylin. The results presented here also support the unconventional notion that distinct conformations of a single endocrine peptide can elicit different responses in different tissues.","journal":"UNC Libraries","year":2021,"id":212643,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":561080,"name":"N. G. Moss","orcid":null,"position":1,"is_corresponding":false},{"id":803678,"name":"D. P. Zimmer","orcid":null,"position":2,"is_corresponding":false},{"id":803679,"name":"D. A. Riguera","orcid":null,"position":3,"is_corresponding":false},{"id":803680,"name":"M. G. Currie","orcid":null,"position":4,"is_corresponding":false},{"id":803681,"name":"M. F. Goy","orcid":null,"position":5,"is_corresponding":false},{"id":803682,"name":"M. M. Kessler","orcid":null,"position":6,"is_corresponding":false},{"id":400895,"name":"William J. Arendshorst","orcid":null,"position":7,"is_corresponding":false},{"id":803677,"name":"R. M. Solinga","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:52:27.434608Z","pmid":null,"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":[]}