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Presence of glucose/carbohydrate but not other nutrients in the duodenal lumen influences duodenal secretory response to orexin-A
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-97105OAI: oai:DiVA.org:uu-97105DiVA: diva2:171900
Available from: 2008-04-23 Created: 2008-04-23 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Effects of Orexins, Guanylins and Feeding on Duodenal Bicarbonate Secretion and Enterocyte Intracellular Signaling
Open this publication in new window or tab >>Effects of Orexins, Guanylins and Feeding on Duodenal Bicarbonate Secretion and Enterocyte Intracellular Signaling
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The duodenal epithelium secretes bicarbonate ions and this is regarded as the primary defence mechanism against the acid discharged from the stomach. For an efficient protection, the duodenum must also function as a sensory organ identifying luminal factors. Enteroendocrine cells are well-established intestinal “taste” cells that express signaling peptides such as orexins and guanylins. Luminal factors affect the release of these peptides, which may modulate the activity of nearby epithelial and neural cells.

The present thesis considers the effects of orexins and guanylins on duodenal bicarbonate secretion. The duodenal secretory response to the peptides was examined in anaesthetised rats in situ and the effects of orexin-A on intracellular calcium signaling by human as well as rat duodenal enterocytes were studied in vitro.

Orexin-A, guanylin and uroguanylin were all stimulants of bicarbonate secretion. The stimulatory effect of orexin-A was inhibited by the OX1-receptor selective antagonist SB-334867. The muscarinic antagonist atropine on the other hand, did not affect the orexin-A-induced secretion, excluding involvement of muscarinic receptors. Orexin-A induced calcium signaling in isolated duodenocytes suggesting a direct effect at these cells. Interestingly, orexin-induced secretion and calcium signaling as well as mucosal orexin-receptor mRNA and OX1-receptor protein levels were all substantially downregulated in overnight fasted rats compared with animals with continuous access to food. Further, secretion induced by Orexin-A was shown to be dependent on an extended period of glucose priming.

The uroguanylin-induced bicarbonate secretion was reduced by atropine suggesting involvement of muscarinic receptors. The melatonin receptor antagonist luzindole attenuated the secretory response to intra-arterially administered guanylins but had no effect on secretion when the guanylins were given luminally.

In conclusion, the results suggest that orexin-A as well as guanylins may participate in the regulation of duodenal bicarbonate secretion. Further, the duodenal orexin system is dependent on the feeding status of the animals.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 337
Keyword
Physiology, alkaline secretion, carbohydrates, central nervous system, cholinergic stimulation, duodenum, enteric nervous system, enterochromaffin cell, fasting, feeding, glucose, guanylyl cyclase C, humans, hypocretin, intra-arterial, in situ, intracerebroventricular, luminal acid, luzindole, orexin-B, SB-334867, Fysiologi
Identifiers
urn:nbn:se:uu:diva-8664 (URN)978-91-554-7173-6 (ISBN)
Public defence
2008-05-15, B21, Uppsala Biomedicinska Centrum (BMC), Norra vägen, Uppsala, 13:15
Opponent
Supervisors
Available from: 2008-04-23 Created: 2008-04-23Bibliographically approved

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