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.
Vagal neural crest-derived precursors of the enteric nervous system colonize the bowel by descending within the enteric mesenchyme. Perpendicular secondary migration, toward the mucosa and into the pancreas, result, respectively, in the formation of submucosal and pancreatic ganglia. We tested the hypothesis that netrins guide these secondary migrations. Studies using RT-PCR, in situ hybridization, and immunocytochemistry indicated that netrins (netrins-1 and -3 mice and netrin-2 in chicks) and netrin receptors [deleted in colorectal cancer (DCC), neogenin, and the adenosine A2b receptor] are expressed by the fetal mucosal epithelium and pancreas. Crest-derived cells expressed DCC, which was developmentally regulated. Crest-derived cells migrated out of explants of gut toward cocultured cells expressing netrin-1 or toward cocultured explants of pancreas. Crest-derived cells also migrated inwardly toward the mucosa of cultured rings of bowel. These migrations were specifically blocked by antibodies to DCC and by inhibition of protein kinase A, which interferes with DCC signaling. Submucosal and pancreatic ganglia were absent at E12.5, E15, and P0 in transgenic mice lacking DCC. Netrins also promoted the survival/development of enteric crest-derived cells. The formation of submucosal and pancreatic ganglia thus involves the attraction of DCC-expressing crest-derived cells by netrins.
We tested the hypothesis that a subset of enteric neurons is glucoresponsive and expresses ATP-sensitive K ϩ (K ATP ) channels. The immunoreactivities of the inwardly rectifying K ϩ channel 6.2 (Kir6.2) and the sulfonylurea receptor (SUR), now renamed SUR1, subunits of pancreatic -cell K ATP channels, were detected on cholinergic neurons in the guinea pig ileum, many of which were identified as sensory by their costorage of substance P and/or calbindin. Glucoresponsive neurons were distinguished in the myenteric plexus because of the hyperpolarization and decrease in membrane input resistance that were observed in response to removal of extracellular glucose. The effects of no-glucose were reversed on the reintroduction of glucose or by the K ATP channel inhibitor tolbutamide. No reversal of the hyperpolarization was observed when Dmannoheptulose, a hexokinase inhibitor, was present on the reintroduction of glucose. Application of the K ATP channel opener diazoxide or the ob gene product leptin mimicked the effect of glucose removal in a reversible manner; moreover, hyperpolarizations evoked by either agent were inhibited by tolbutamide. Glucoresponsive neurons displayed leptin receptor immunoreactivity, which was widespread in both enteric plexuses. Superfusion of diazoxide inhibited fast synaptic activity in myenteric neurons, via activation of presynaptic K ATP channels. Diazoxide also produced a decrease in colonic motility. These experiments demonstrate for the first time the presence of glucoresponsive neurons in the gut. We propose that the glucose-induced excitation of these neurons be mediated by inhibition of K ATP channels. The results support the idea that enteric K ATP channels play a role in glucose-evoked reflexes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.