title: Evidence for a role of endogenous nesfatin-1 in the control of water drinking.
abstract: Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is produced in several brain areas known to be important in neuroendocrine, autonomic and metabolic function, including the hypothalamus and medulla. The hallmark action of the peptide is its ability at picomole doses to inhibit food and water intake in rodents and, indeed, the effect on water intake is more pronounced than that on food intake. In preliminary studies, we observed a decrease in hypothalamic NucB2 expression in response to overnight water deprivation even when food was present, which reversed when water was returned to the animals. We therefore hypothesised that the effect of nesfatin-1 on water drinking was independent of its anorexigenic action. Indeed, rats administered nesfatin-1 i.c.v. consumed significantly less water than controls in response to a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles after 18 h of fluid restriction (food present), or in response to a hypertonic challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1 significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic paraventricular nucleus and resulted in exaggerated drinking responses to angiotensin II. The results obtained in the present study suggest that locally produced nesfatin-1 may be an important component of the hypothalamic mechanisms controlling fluid and electrolyte homeostasis.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA. gyosten@slu.edu
authors.forename: G L C
authors.initials: GL
authors.lastname: Yosten
authors.forename: L
authors.initials: L
authors.lastname: Redlinger
authors.forename: W K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000235:genetics*; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000080866:Nucleobindins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013894:Thirst / Q000187:drug effects / Q000502:physiology; D014018:Tissue Distribution / Q000187:drug effects; D014868:Water Deprivation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D000804:Angiotensin II