Hypothalamic Actions of Neuromedin U

• DOI: 10.1210/en.2002-220308
• Publication Date: 2002-10-24T14:03:26Z
• Authors: A. M. Wren; C. J. Small; C. R. Abbott; P. H. Jethwa; A. R. Kennedy; K. G. Murphy; S. A. Stanley; A. N. Zollner; M. A. Ghatei; S. R. Bloom
• Keywords: Leptin; Male; 0301 basic medicine; 2. Zero hunger; Behavior, Animal; Microinjections; Corticotropin-Releasing Hormone; Neuropeptides; Hypothalamus; Motor Activity; Grooming; Rats; Arginine Vasopressin; Eating; 03 medical and health sciences; Adrenocorticotropic Hormone; Pituitary Gland; Adrenal Glands; Animals; Rats, Wistar; Corticosterone; Injections, Intraventricular; Paraventricular Hypothalamic Nucleus

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.