title: Dietary salt regulates uroguanylin expression and signaling activity in the kidney, but not in the intestine.
abstract: The peptide uroguanylin (Ugn) is expressed at significant levels only in intestine and kidney, and is stored in both tissues primarily (perhaps exclusively) as intact prouroguanylin (proUgn). Intravascular infusion of either Ugn or proUgn evokes well-characterized natriuretic responses in rodents. Furthermore, Ugn knockout mice display hypertension and salt handling deficits, indicating that the Na(+) excretory mechanisms triggered when the peptides are infused into anesthetized animals are likely to operate under normal physiological conditions, and contribute to electrolyte homeostasis in conscious animals. Here, we provide strong corroborative evidence for this hypothesis, by demonstrating that UU gnV (the rate of urinary Ugn excretion) approximately doubled in conscious, unrestrained rats consuming a high-salt diet, and decreased by ~15% after salt restriction. These changes in UU gnV were not associated with altered plasma proUgn levels (shown here to be an accurate index of intestinal proUgn secretion). Furthermore, enteric Ugn mRNA levels were unaffected by salt intake, whereas renal Ugn mRNA levels increased sharply during periods of increased dietary salt consumption. Together, these data suggest that diet-evoked Ugn signals originate within the kidney, rather than the intestine, thus strengthening a growing body of evidence against a widely cited hypothesis that Ugn serves as the mediator of an entero-renal natriuretic signaling axis, while underscoring a likely intrarenal natriuretic role for the peptide. The data further suggest that intrarenal Ugn signaling is preferentially engaged when salt intake is elevated, and plays only a minor role when salt intake is restricted.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Fellner
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Moss
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina mgoy@med.unc.edu.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Goy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045265:Natriuretic Peptides / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D045265:Natriuretic Peptides; D012982:Sodium, Dietary; C084362:uroguanylin
keywords: Dietary salt; entero‐renal endocrine axis; natriuretic peptide; sodium homeostasis