Intracisternal injection of orexin-A prevents ethanol-induced gastric mucosal damage in rats.
BACKGROUND
Accumulating evidence indicates that orexin-A in the brain stimulates vagal flow projecting to the stomach. Since the vagal system plays an important role in gastric mucosal integrity, we hypothesized that orexin-A in the brain might have a gastroprotective action.


METHODS
We examined the effect of centrally administered orexin-A on the development of gastric mucosal damage evoked by ethanol and its possible mechanism of action in rats.


RESULTS
Intracisternal but not intraperitoneal injection of orexin-A significantly inhibited the severity of gastric mucosal damage by 70% ethanol in a dose-dependent manner, suggesting that orexin-A acts in the brain to prevent ethanol-induced gastric mucosal damage. The antiulcer action was observed in rats administered with orexin-A centrally but not orexin-B, indicating that the action is mediated through orexin 1 receptors. The gastroprotective action of centrally administered orexin-A was blocked by pretreatment with atropine, Nomega-nitro-L-arginine methylester, or indomethacin.


CONCLUSIONS
These results suggest that orexin-A acts on orexin 1 receptors in the brain to exert a gastroprotective action against ethanol. The vagal muscarinic system, nitric oxide, and prostaglandins may mediate the cytoprotective action of centrally administered orexin-A.
Yamada
Hiroto
H
Department of General Medicine, Asahikawa Medical College, 4-5 Nishikagura, Asahikawa, Hokkaido 078-8510, Japan.
Tanno
Satoshi
S
Takakusaki
Kaoru
K
Okumura
Toshikatsu
T
D000818:Animals; D001921:Brain / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000517:prevention & control*; D007267:Injections; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage*; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D018013:Receptors, Neuropeptide / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D000431:Ethanol