Orexin Synthesis and Response in the Gut

Abstract

Orexin (hypocretin) appears to play a role in the regulation of energy balances. Previous reports have indicated that orexin-containing neurons are found only in the lateral hypothalamic (LH) area. We show that a subset of neurons in the gut which also express leptin receptors display orexin-like immunoreactivity and express functional orexin receptors. Orexin excites secretomotor neurons in the guinea pig submucosal plexus and increases motility. Moreover, fasting upregulates the phosphorylated form of cAMP response element-binding protein (pCREB) in orexin-immunoreactive neurons, indicating a functional response to food status in these cells. Together, these data suggest that orexin in the gut may play an even more intimate role in regulating energy homeostasis than it does in the CNS.

Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in mice

“…7. Previous studies have demonstrated that OXR1 is clearly expressed in pancreatic islets and beta cells of pigs, rats and mice [9][10][11]. Here, we showed that OXA influenced insulin secretion in pancreatic islets through OXR1, but not OXR2.…”

“…OXRs have been demonstrated not only in central neurons but also in some peripheral endocrine cells. Recent studies have demonstrated that OXR1 is expressed in the pancreatic alpha and beta cells of pigs, rats and mice [9][10][11] and in human and rat adipocytes [12,13]. Therefore, it is likely that orexins contribute to important endocrine functions.…”

Expression of Orexin A and Its Receptor 1 in the Vestibular Glands of the Cattle Genital Tract

“…Recent studies demonstrated that orexins and their receptors are expressed in the NE cellular population of the digestive mucosa, where they play a role in the regulation of gut motility, blood flow, and epithelial secretion (Kirchgessner and Liu, 1999;Ehrström et al, 2005). In this study, the expression of oxA and of its highly specific receptor ox1R in the vestibular glands of the cattle genital tract was assessed.…”

“…The coexistence of 5-HT and oxA has been demonstrated in other organs of the mammalian body (Muraki et al, 2004;Wang et al, 2005;Tao et al, 2006). The human bowel contains NE cells costoring 5-HT and oxA whose secretion could stimulate both intrinsic and extrinsic primary afferent neurons (Kirchgessner and Liu, 1999). The peptide oxA has recently been found in NE cells of the cattle urethra (Russo et al, 2008), where 5-HT is widespread diffused.…”

“…The orexins are widely diffused in the neurons of the central nervous system Nambu et al, 1999) and in the intrinsic innervation of the gut (Kirchgessner and Liu, 1999). Recently, their presence has also been demonstrated in endocrine cytotypes belonging to the gastrointestinal tract, pancreas, adrenal glands, and testis (Randewa et al, 2001;Karteris et al, 2004;Barreiro et al, 2005;Ehrström et al, 2005;Zhang et al, 2005).…”