Effects of Orexins, Guanylins and Feeding on Duodenal Bicarbonate Secretion and Enterocyte Intracellular Signaling

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MARC

Bengtsson, Magnus Wilhelm,1977-Uppsala universitet,Institutionen för neurovetenskap (author)

Effects of Orexins, Guanylins and Feeding on Duodenal Bicarbonate Secretion and Enterocyte Intracellular Signaling

BookEnglish2008

Publisher, publication year, extent ...

Uppsala :Acta Universitatis Upsaliensis,2008
70 s.
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-8664
ISBN:9789155471736
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8664URI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

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Subject category:vet swepub-contenttype
Subject category:dok swepub-publicationtype

Series

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;337

Notes

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.

Subject headings and genre

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

Added entries (persons, corporate bodies, meetings, titles ...)

Flemström, Gunnar (thesis advisor)
Nylander, Olof (thesis advisor)
Åkerman, Karl E. O. (thesis advisor)
Hellström, Per M.,ProfessorInstitutionen för medicin, Karolinska Institutet, Stockholm (opponent)
Uppsala universitetInstitutionen för neurovetenskap (creator_code:org_t)

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