Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin

Abstract

. Short fasting dramatically decreases rat duodenal secretory responsiveness to orexin A but not to VIP or melatonin. Am J Physiol Gastrointest Liver Physiol 285: G1091-G1096, 2003. First published July 17, 2003 10.1152/ajpgi.00193.2003Orexins 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 HCO 3 Ϫ 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 ⅐ kg Ϫ1 ⅐ h Ϫ1 ) 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 ⅐ kg Ϫ1 ⅐ h Ϫ1 ) required for stimulation of the secretion. In contrast, the secretory responses to VIP (50-1,000 pmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) and melatonin (20-200 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) 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.bethanochol; bicarbonate secretion; duodenal mucosal protection; food deprivation; vasoactive intestinal polypeptide OREXINS WERE FIRST ISOLATED as hypothalamic appetiteincreasing peptides (9, 38) and appear to be involved in short-term regulation of feeding rather than long-term regulation of body weight (6, 46). Effects are mediated via two G protein-coupled receptors denoted OX 1 and OX 2 (21, 24). Orexins and receptors were also recently discovered in numerous endocrine (enterochromaffin) cells in the gastrointestinal tract and are present in the enteric nerves (21,24,27). The role of these compounds in peripheral regulation of intestinal function has, however, not been investigated in detail. Orexin cells in the hypothalamus are stimulated by fasting and inhibited by feeding (6). By tradition (32), experimental studies of gastrointestinal physiology and pathophysiology in humans and in intact animals have been conducted after overnight fast. Because the presence of food itself has a considerable effect of intestinal function (14), we have compared the actions of orexins and other intestinal se...

Food-induced expression of orexin receptors in rat duodenal mucosa regulates the bicarbonate secretory response to orexin-A

“…We showed earlier that short fasting also altered the sensitivity (but not the magnitude) of cholinergic stimulation of secretion (18). A role for cholinergic mechanisms in orexin action on the contractility of guinea pig ileum has previously been shown (33) and many of the central actions of orexins are mediated by cholinergic mechanisms (40).…”

“…These findings provide evidence that orexininduced stimulation of the duodenal secretion is independent of cholinergic pathways. In contrast to orexin-A and bethanechol, rises in HCO 3 Ϫ secretion in response to serotonin (39), melatonin, or vasoactive intestinal polypeptide (18) are not altered by overnight food deprivation. This means that certain pathways for stimulation of intestinal secretion are selectively downregulated.…”

“…A short period of food deprivation was recently shown to profoundly modulate the small intestinal secretory response to orexin-A. Stimulation of duodenal alkaline secretion was thus abolished by overnight fasting (17,18). Food deprivation for a longer period of time (2 days) did not affect preproorexin gene expression or hypothalamic orexin-A peptide levels in lactating rats, but there was a significant increase in hypothalamic orexin-B levels in these animals (6).…”

Melatonin‐evoked in vivo secretion of protein and amylase from the parotid gland of the anaesthetised rat

“…Flemström et al. [33] have drawn attention to the fact that overnight fasting in rats may result in a 100‐fold decrease in the sensitivity to secretagogues when it comes to evoking duodenal bicarbonate secretion. In the present study, almost all the rats had been fasted over night.…”

Epithelial Cells and Their Neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells

“…Muscarinic pathways may, in part, be involved. the duodenal alkaline secretion in rats (7). However, stimulation occurred only in animals that had continuous access to their regular food.…”