Orexins activate histaminergic neurons via the orexin 2 receptor.
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.
Yamanaka
Akihiro
A
Department of Pharmacology, Institute of Basic Medical Sciences, Tsukuba, Ibaraki, 305-8575, Japan.
Tsujino
Natsuko
N
Funahashi
Hisayuki
H
Honda
Kazuki
K
Guan
Jian-lian
JL
Wang
Quing-Ping
QP
Tominaga
Makoto
M
Goto
Katsutoshi
K
Shioda
Seiji
S
Sakurai
Takeshi
T
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*
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