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Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
2003 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 285, no 6, G1091-G1096 p.Article in journal (Refereed) Published
Abstract [en]

Orexins are involved in the central nervous control of appetite and behavior, and in addition, they are present in endocrine cells and/or neurons in the intestine. The role of these peptides in peripheral regulation of intestinal secretion has not been investigated. We thus compared the effects of orexin A and some established secretagogues on duodenal HCO3- secretion in fed rats with effects in rats exposed to short (overnight) food deprivation. Rats were anesthetized with thiobarbiturate, a 12-mm segment of proximal duodenum with intact blood supply was cannulated in situ, and the alkaline secretion was titrated by pH stat. Secretagogues were supplied specifically to the duodenum by close intra-arterial infusion. Orexin A (60-600 pmol·kg-1·h-1) caused marked and dose-dependent stimulation of the duodenal secretion in fed animals but did not affect secretion in overnight food-deprived animals. Similarly, short fasting caused a 100-fold increase in the amount of the muscarinic agonist bethanechol (from 50 to 5,000 nmol·kg-1·h-1) required for stimulation of the secretion. In contrast, the secretory responses to VIP (50-1,000 pmol·kg-1·h-1) and melatonin (20-200 nmol·kg-1·h-1) were not affected. The appetite-regulating peptide orexin A is thus a stimulant of intestinal secretion, but the response to this peptide as well as the muscarinic agonist bethanechol is markedly dependent on previous intake of food. Overnight fasting is a standard experimental procedure in studies of gastrointestinal function and pathophysiology in humans and animals. Studies made on neuroendocrine control of intestinal secretion may require reevaluation with respect to feeding status.

Place, publisher, year, edition, pages
2003. Vol. 285, no 6, G1091-G1096 p.
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-90659DOI: 10.1152/ajpgi.00193.2003OAI: oai:DiVA.org:uu-90659DiVA: diva2:163100
Available from: 2003-09-09 Created: 2003-09-09 Last updated: 2017-12-14Bibliographically approved
In thesis
1. The Duodenal Mucosal Bicarbonate Secretion: Role of Melatonin in Neurohumoral Control and Cellular Signaling
Open this publication in new window or tab >>The Duodenal Mucosal Bicarbonate Secretion: Role of Melatonin in Neurohumoral Control and Cellular Signaling
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The duodenal lumen is exposed to aggressive factors with a high potential to cause damage to the mucosa. Bicarbonate secretion by the duodenal mucosa is accepted as the primary important defense mechanism against the hydrochloric acid intermittently expelled from the stomach.

The present thesis concerns the influence of the central nervous system and the effects of the hormone melatonin on bicarbonate secretion in anesthetized rats in vivo. Effects of melatonin on intracellular calcium signaling by duodenal enterocyte in vitro were examined in tissues of both human and rat origin. The main findings were as follows:

Melatonin is a potent stimulant of duodenal mucosal bicarbonate secretion and also seems to be involved in the acid-induced stimulation of the secretion. Stimulation elicited in the central nervous system by the α1-adrenoceptor agonist phenylephrine induced release of melatonin from the intestinal mucosa and a four-fold increase in alkaline secretion. The melatonin antagonist luzindole abolished the duodenal secretory response to administered melatonin and to central nervous phenylephrine but did not influence the release of intestinal melatonin. Central nervous stimulation was also abolished by synchronous ligation of the vagal trunks and the sympathetic chains at the sub-laryngeal level.

Melatonin induced release of calcium from intracellular stores and also influx of extracellular calcium in isolated duodenal enterocytes. Enterocytes in clusters functioned as a syncytium.

Overnight fasting rapidly and profoundly down-regulated the responses to the duodenal secretagogues orexin-A and bethanechol but not those to melatonin or vasoactive intestinal polypeptide.

In conclusion, the results strongly suggest that intestinal melatonin plays an important role in central nervous elicited stimulation of duodenal mucosal bicarbonate secretion. Sensitivity of this alkaline secretion to some peripheral stimulators markedly depends on the feeding status.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 71 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1277
Keyword
Physiology, alkaline secretion, central nervous system, duodenal enterocyte, duodenal ulcer, duodenum, enterochromaffin cell, human, intraarterial, intracellular calcium, intracerebroventricular, melatonin, rat, vagal nerve, Fysiologi
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-3521 (URN)91-554-5688-X (ISBN)
Public defence
2003-10-03, B42, BMC, Uppsala, 09:15
Opponent
Supervisors
Available from: 2003-09-09 Created: 2003-09-09Bibliographically approved

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Flemström, GunnarSjöblom, Markus

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