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Orexins in the Brain-Gut Axis

Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098

Correspondence: Address all correspondence and requests for reprints to: Annette L. Kirchgessner, Ph.D., Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 29, Brooklyn, New York 11203-2098. E-mail: akirchgessner{at}netmail.hscbklyn.edu

Orexins (hypocretins) are a novel pair of neuropeptides implicated in the regulation of energy balances and arousal. Previous reports have indicated that orexins are produced only in the lateral hypothalamic area, although orexin-containing nerve fibers were observed throughout the neuroaxis. Recent evidence shows that orexins and functional orexin receptors are found in the periphery. Vagal and spinal primary afferent neurons, enteric neurons, and endocrine cells in both the gut and pancreas display orexin- and orexin receptor-like immunoreactivity. Orexins excite secretomotor neurons in the guinea pig gut and modulate gastric and intestinal motility and secretion. In addition, orexins modulate hormone release from pancreatic endocrine cells. Moreover, fasting up-regulates the phosphorylated form of cAMP response element binding protein in orexin-immunoreactive enteric neurons, indicating a functional response to food status in these cells. The purpose of this article is to summarize evidence for the existence of a brain-gut network of orexin-containing cells that appears to play a role in the acute regulation of energy homeostasis.

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