title: Orexin stimulates breathing via medullary and spinal pathways.
abstract: A central neuronal network that regulates respiration may include hypothalamic neurons that produce orexin, a peptide that influences sleep and arousal. In these experiments, we investigated 1) projections of orexin-containing neurons to the pre-Botzinger region of the rostral ventrolateral medulla that regulates rhythmic breathing and to phrenic motoneurons that innervate the diaphragm; 2) the presence of orexin A receptors in the pre-Botzinger region and in phrenic motoneurons; and 3) physiological effects of orexin administered into the pre-Botzinger region and phrenic nuclei at the C3-C4 levels. We found orexin-containing fibers within the pre-Botzinger complex. However, only 0.5% of orexin-containing neurons projected to the pre-Botzinger region, whereas 2.9% of orexin-containing neurons innervated the phrenic nucleus. Neurons of the pre-Botzinger region and phrenic nucleus stained for orexin receptors, and activation of orexin receptors by microperfusion of orexin in either site produced a dose-dependent, significant (P <0.05) increase in diaphragm electromyographic activity. These data indicate that orexin regulates respiratory activity and may have a role in the pathophysiology of sleep-related respiratory disorders.
authors.affiliation: Dept. of Anatomy, Howard Univ. College of Medicine, 520 W St., NW, Washington, DC 20059, USA. jyoung@howard.edu
authors.forename: John K
authors.initials: JK
authors.lastname: Young
authors.forename: Mingfei
authors.initials: M
authors.lastname: Wu
authors.forename: Kebreten F
authors.initials: KF
authors.lastname: Manaye
authors.forename: Prabha
authors.initials: P
authors.lastname: Kc
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Allard
authors.forename: Serdia O
authors.initials: SO
authors.lastname: Mack
authors.forename: Musa A
authors.initials: MA
authors.lastname: Haxhiu
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000008:administration & dosage*; D064446:Orexin Receptors; D000068797:Orexins; D010791:Phrenic Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide