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Release of regulatory gut peptides somatostatin, neurotensin and vasoactive intestinal peptide by acid and hyperosmolal solutions in the intestine in conscious rats
Department of Medicine, Gastroenterology and Hepatology unit, Karolinska Institutet, Karolinska University Hospital.
Department of Medicine, Gastroenterology and Hepatology unit, Karolinska Institutet, Karolinska University Hospital.
Department of Clinical Chemistry, Linköping University.
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital.
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2009 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 152, no 1-3, 8-12 p.Article in journal (Refereed) Published
Abstract [en]

The impact of exposure of the intestinal mucosa to acid and hyperosmolal solutions on the release of the inhibitory gut peptides somatostatin (SOM), neurotensin (NT) and vasoactive intestinal peptide (VIP) was studied in conscious rats during pentagastrin-stimulated gastric acid secretion. The animals were equipped with a chronic gastric fistula to measure acid secretion and a jejunal Thiry-Vella loop for intestinal challenge with saline, hydrochloric acid (HCl, 200 mmol L(-1)) or hyperosmolal polyethylene glycol (PEG, 1200 mOsm kg(-1)). Gut peptide concentrations were measured in intestinal perfusates, and in plasma samples collected during stimulated acid secretion, and at the end of experiments with luminal challenge of the loops. After pentagastrin-stimulation acid secretion was dose-dependently inhibited by intravenous administration of the gastrin receptor antagonist gastrazole, as well as ranitidine and esomeprazole by maximally 73+/-10%; 95+/-3%; 90+/-10%, respectively. Acid perfusion of the Thiry-Vella loop caused a prominent release of SOM both to the lumen (from 7.2+/-5.0 to 1279+/-580 pmol L(-1)) and to the circulation (from 18+/-5.2 to 51+/-9.0 pmol L(-1)) simultaneously with an inhibition of gastric acid secretion. The release of NT and VIP was not affected to the same extent. PEG perfusion of the loop caused a release of SOM as well as NT and VIP, but less. Simultaneously acid secretion was slightly decreased. In conclusion, intestinal perfusion with acid or hyperosmolal solutions mainly releases SOM, which seems to exert a major inhibitory action in the gut, as shown by inhibition of acid secretion. The other peptides NT and VIP also participate in this action but to a much lesser degree. The operative pathways of these gut peptides hence involve both endocrine (SOM) and paracrine actions (SOM, NT, VIP) in order to exert inhibitory functions on the stomach. The inhibitory action of gastrazole, was in a similar range as that of SOM implying that physiological acid-induced inhibition of gastric acid may primarily be exerted through inhibition of gastrin endocrine secretion.

Place, publisher, year, edition, pages
2009. Vol. 152, no 1-3, 8-12 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:rkh:diva-1431DOI: 10.1016/j.regpep.2008.10.002PubMedID: 18992283OAI: oai:DiVA.org:rkh-1431DiVA: diva2:787472
Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2015-02-10Bibliographically approved
In thesis
1. Gastric acid secretion and gut peptides: mechanisms involved in inflammatory response
Open this publication in new window or tab >>Gastric acid secretion and gut peptides: mechanisms involved in inflammatory response
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The regulation of gastric acid secretion is complex and involves endocrine, paracrine, and neurocrine mechanisms. Among these, the interconnecting cross-talk between different gut peptides is an important part in the control of acid secretion. The aims of this thesis were (1) to develop a new method of measuring intragastric pH for prolonged periods of time, and (2) apply developed and in-use methods using different substances and their impact on gastric acid secretion in vivo experiments on rats. (3) To study the changes in acid output and the migrating motor complex (MMC) when subjected to different substances, and (4) to further study the alterations in expression of different gut peptides in tissue samples in vitro, and the impact of inflammation in the gut. The novel Bravo model developed gave reliable recordings compared to the chronic fistula model. The pH rose during treatment with esomeprazole and the acid output in the fistula model decreased accordingly. Gut peptides ghrelin and somatostatin increased in plasma when subjected to esomeprazole treatment, while gastrin remained unchanged. Ghrelin administered in bolus doses increased the intragastric pH in accordance with previous experiments. The gut peptides somatostatin, neurotensin, and vasoactive intestinal peptide increased during pentagastrin-stimulated infusion and challenge with hydrochloric acid and polyethylene glycol both in plasma and intestinal perfusate, though the most pronounced elevation was seen in perfusate and with somatostatin. Gastrazole gave the most extensive inhibitory effect on acid secretion compared to ranitidine and esomeprazole. The CCK2-receptor antagonist YF476 inhibited acid secretion long-term and increased concentrations of ghrelin and somatostatin in plasma, but gastrin remained low. Tissue mRNA content of the peptides and their receptors were unchanged except for the ghrelin receptor. When subdued to NSAID gastrin, CCK2-receptor and iNOS increased in mRNA expression while other peptides and receptors were unchanged. Administration of NPS evoked a response in the MMC pattern with irregular spiking and prolonged cycle length of the activity fronts, and the mRNA expression of iNOS, TNF, and IL-1ß increased in the tissue. In conclusion, The Bravo model can be used as a complement to the chronic fistula model for measurements of pH. The regulation of gastric acid secretion is not only limited to the stomach, but also present in the smaller intestine where release of somatostatin seems to be most important. Different mechanisms are involved in the blockage of acid secretion when subjected to YF476, but under NSAID treatment the expression of gastrin and its receptor CCK2 increase and COX- 2 is activated which demonstrates a novel pathway for the study of gastric ulcerations. NPS, a novel neuropeptide influences the gastric motility and could have a role in inflammatory responses seen in the changes in the migrating motor complex and inflammatory markers iNOS, TNF, and IL-1ß.

Place, publisher, year, edition, pages
Stockholm: Department of Medicine, Karolinska Institutet, 2010. 97 p.
National Category
Basic Medicine
Identifiers
urn:nbn:se:rkh:diva-1434 (URN)978-91-7457-063-2 (ISBN)
Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2015-02-10Bibliographically approved

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