Central orexin plays a role in the regulation of gut functions

Abstract

Orexins are neuropeptides that are localized in neurons within the lateral hypothalamic area and regulate feeding behavior. Accumulating evidence have shown that orexins acts centrally to regulate a wide variety of body functions including gastrointestinal functions. The aim of this review is to summarize relevant findings on brain orexins and a digestive system, and discuss the pathophysiological roles of the peptides with special reference to functional gastrointestinal disorders. Exogenously administered orexin or endogenously released orexin in the brain potently stimulates gastric acid secretion, and gastric and colonic motility in conscious rats. In addition, central orexin induces an antinociceptive action against colonic distension. Pretreatment with either dopamine, adenosine A1 or cannabinoid antagonist potently blocked the centrally injected orexin-A-induced antinociceptive action. These results suggest that dopaminergic, adenosinergic or cannabinoid signaling may be involved in the central orexin-induced antinociceptive action against colonic distension. From these evidence, we would like to make a hypothesis that decreased orexin signaling in the brain may play a role in the pathophysiology in a part of patients with functional gastrointestinal disorders such as irritable bowel syndrome (IBS) who are frequently accompanied with the inhibition of gut function such as GI motility and visceral hypersensitivity.