title: Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus.
abstract: Ghrelin, a gastrointestinal peptide, stimulates feeding when administered peripherally. Blockade of the vagal afferent pathway abolishes ghrelin-induced feeding, indicating that the vagal afferent pathway may be a route conveying orexigenic ghrelin signals to the brain. Here, we demonstrate that peripheral ghrelin signaling, which travels to the nucleus tractus solitarius (NTS) at least in part via the vagus nerve, increases noradrenaline (NA) in the arcuate nucleus of the hypothalamus, thereby stimulating feeding at least partially through alpha-1 and beta-2 noradrenergic receptors. In addition, bilateral midbrain transections rostral to the NTS, or toxin-induced loss of neurons in the hindbrain that express dopamine beta hydroxylase (an NA synthetic enzyme), abolished ghrelin-induced feeding. These findings provide new evidence that the noradrenergic system is necessary in the central control of feeding behavior by peripherally administered ghrelin.
authors.affiliation: Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan. dateyuka@med.miyazaki-u.ac.jp
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimbara
authors.forename: Shuichi
authors.initials: S
authors.lastname: Koda
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.forename: Takanori
authors.initials: T
authors.lastname: Ida
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ishizuka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Haruaki
authors.initials: H
authors.lastname: Kageyama
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000818:Animals; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012249:Rhombencephalon / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054439:Ghrelin; D009478:Neuropeptide Y; D036361:Peptide Hormones; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine