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1 Division of Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden
* To whom correspondence should be addressed. E-mail: Gunnar.Flemstrom{at}fysiologi.uu.se.
Orexins are involved in the central nervous control of appetite and behavior and are, in addition, 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 titrated by pH-stat. Secretagogues were supplied specifically to the duodenum by close intra-arterial infusion. Orexin-A (60-600 pmolkg-1h-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 an 100-fold increase in the amount of the muscarinic agonist bethanechol (from 50 to 5,000 nmolkg-1h-1) required for stimulation of the secretion. In contrast, the secretory responses to vasoactive intestinal polypeptide (50-1,000 pmolkg-1h-1) and melatonin (20-200 nmolkg-1h-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 and may require re-evaluation with respect to feeding status.
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