title: Orexins activate histaminergic neurons via the orexin 2 receptor.
abstract: Orexins (orexin A and B) are recently identified neuropeptides implicated in the regulation of vigilance states and energy homeostasis. We have shown here the physiological significance of histaminergic neurons in the orexin-induced arousal responses. Immunohistochemical and electron microscopic techniques revealed direct synaptic interaction between orexin-immunoreactive nerve terminals and histidine decarboxylase-immunoreactive neurons in the TMN. Electrophysiological study revealed that orexins dose-dependently activate histaminergic neurons, which were freshly isolated from rats TMN region. To further evaluate, we examined the effect of pyrilamine, an H(1) receptor antagonist, on orexin-induced arousal response in rats. Simultaneously recordings of electroencephalograph and electromyograph showed that intracerebroventricular infusion of orexin A significantly increased the awake state in the light phase. Central application of pyrilamine significantly inhibited this response. These results strongly suggest that activation of histaminergic neurons by orexins might be important for modulation of the arousal.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tsujino
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Funahashi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Honda
authors.forename: Jian-lian
authors.initials: JL
authors.lastname: Guan
authors.forename: Quing-Ping
authors.initials: QP
authors.lastname: Wang
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Goto
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006632:Histamine / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D006634:Histamine H1 Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D006632:Histamine; D006640:Histidine Decarboxylase; D011738:Pyrilamine