Abstract
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, N ω-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.
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Yamada, H., Tanno, S., Takakusaki, K. et al. Intracisternal injection of orexin-A prevents ethanol-induced gastric mucosal damage in rats. J Gastroenterol 42, 336–341 (2007). https://doi.org/10.1007/s00535-007-2007-2
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DOI: https://doi.org/10.1007/s00535-007-2007-2