title: Effects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagogues.
abstract: Studies of gastrointestinal physiology in humans and intact animals are usually conducted after overnight fast. We compared the effects of orexin-A, vasoactive intestinal polypeptide (VIP), melatonin, serotonin, uroguanylin, ghrelin and prostaglandin E(2) (PGE(2)) on duodenal bicarbonate secretion in fed and overnight fasted animals. This review is a summary of our findings. Secretagogues were administered by intra-arterial infusion or luminally (PGE(2)). Enterocyte intracellular calcium ([Ca(2+)](i)) signalling was studied by fluorescence imaging. Total RNA was extracted, reverse transcripted to cDNA and expression of orexin receptors measured by quantitative real-time PCR. Orexin-A stimulates the duodenal secretion in continuously fed animals but not in food-deprived animals. Similarly, short-term fasting causes a 100-fold decrease in the amount of the muscarinic agonist bethanechol required for stimulation of secretion. In contrast, fasting does not affect secretory responses to intra-arterial VIP, melatonin, serotonin, uroguanylin and ghrelin, or that to luminal PGE(2). Orexin-A induces [Ca(2+)](i) signalling in enterocytes from fed rats but no significant [Ca(2+)](i) responses occur in enterocytes from fasted animals. In addition, overnight fasting decreases the expression of mucosal orexin receptors. Short-term food deprivation thus decreases duodenal expression of orexin receptors and abolishes the secretory response to orexin-A as well as orexin-A-induced [Ca(2+)](i) signalling. Fasting, furthermore, decreases mucosal sensitivity to bethanechol. The absence of declines in secretory responses to other secretagogues tested strongly suggests that short-term fasting does not affect the secretory capacity of the duodenal mucosa in general. Studies of intestinal secretion require particular evaluation with respect to feeding status.
authors.affiliation: Division of Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden. gunnar.flemstrom@neuro.uu.se
authors.forename: G
authors.initials: G
authors.lastname: Flemström
authors.forename: M W
authors.initials: MW
authors.lastname: Bengtsson
authors.forename: K
authors.initials: K
authors.lastname: Mäkelä
authors.forename: K H
authors.initials: KH
authors.lastname: Herzig
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000008:administration & dosage; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000294:innervation; D054439:Ghrelin / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008550:Melatonin / Q000008:administration & dosage; D045265:Natriuretic Peptides / Q000008:administration & dosage; D009479:Neuropeptides / Q000008:administration & dosage*; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D064446:Orexin Receptors; D000068797:Orexins; D017933:Peripheral Nervous System / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage
chemical_list: D001639:Bicarbonates; D054439:Ghrelin; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D045265:Natriuretic Peptides; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C084362:uroguanylin; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D008550:Melatonin; D015232:Dinoprostone