title: Hypothalamic actions of neuromedin U.
abstract: The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 +/- 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 +/- 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 +/- 1.9 pg/ml; saline, 11.4 +/- 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 +/- 40.5 ng/ml; saline, 129.4 +/- 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 +/- 0.95 pmol/explant; basal, 3.8 +/- 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 +/- 21.8 fmol/explant; basal, 74.5 +/- 7.6; P < 0.01). Leptin stimulated NMU release (141.9 +/- 20.4 fmol/explant; basal, 92.9 +/- 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding.
authors.affiliation: Endocrine Unit, Faculty of Medicine, Imperial College, London W12 0NN, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Wren
authors.forename: C J
authors.initials: CJ
authors.lastname: Small
authors.forename: C R
authors.initials: CR
authors.lastname: Abbott
authors.forename: P H
authors.initials: PH
authors.lastname: Jethwa
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: K G
authors.initials: KG
authors.lastname: Murphy
authors.forename: S A
authors.initials: SA
authors.lastname: Stanley
authors.forename: A N
authors.initials: AN
authors.lastname: Zollner
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006120:Grooming; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D020738:Leptin / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020738:Leptin; D009479:Neuropeptides; D001127:Arginine Vasopressin; C056900:neuromedin U; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone