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

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Fältnamn	Indikatorer	Metadata
000		04304nam a2200589 4500
001		oai:DiVA.org:uu-8664
003		SwePub
008		080423s2008 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
020		a 9789155471736q print
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-86642 URI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a vet2 swepub-contenttype
072	7	a dok2 swepub-publicationtype
100	1	a Bengtsson, Magnus Wilhelm,d 1977-u Uppsala universitet,Institutionen för neurovetenskap4 aut
245	1 0	a Effects of Orexins, Guanylins and Feeding on Duodenal Bicarbonate Secretion and Enterocyte Intracellular Signaling
264	1	a Uppsala :b Acta Universitatis Upsaliensis,c 2008
300		a 70 s.
338		a electronic2 rdacarrier
490	0	a Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,x 1651-6206 ;v 337
520		a 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.
653		a Physiology
653		a alkaline secretion
653		a carbohydrates
653		a central nervous system
653		a cholinergic stimulation
653		a duodenum
653		a enteric nervous system
653		a enterochromaffin cell
653		a fasting
653		a feeding
653		a glucose
653		a guanylyl cyclase C
653		a humans
653		a hypocretin
653		a intra-arterial
653		a in situ
653		a intracerebroventricular
653		a luminal acid
653		a luzindole
653		a orexin-B
653		a SB-334867
653		a Fysiologi
700	1	a Flemström, Gunnar4 ths
700	1	a Nylander, Olof4 ths
700	1	a Åkerman, Karl E. O.4 ths
700	1	a Hellström, Per M.,c Professoru Institutionen för medicin, Karolinska Institutet, Stockholm4 opn
710	2	a Uppsala universitetb Institutionen för neurovetenskap4 org
856	4	u https://uu.diva-portal.org/smash/get/diva2:171902/FULLTEXT01.pdfx primaryx Raw objecty fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:171902/COVER01.pdfy cover
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8664

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