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Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces

Background: In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intes...

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Published in:Gut 2007-09, Vol.56 (9), p.1191-1197
Main Authors: Farré, Ricard, De Vos, Rita, Geboes, Karel, Verbecke, Kristine, Berghe, Pieter Vanden, Depoortere, Inge, Blondeau, Kathleen, Tack, Jan, Sifrim, Daniel
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container_end_page 1197
container_issue 9
container_start_page 1191
container_title Gut
container_volume 56
creator Farré, Ricard
De Vos, Rita
Geboes, Karel
Verbecke, Kristine
Berghe, Pieter Vanden
Depoortere, Inge
Blondeau, Kathleen
Tack, Jan
Sifrim, Daniel
description Background: In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces. Methods: Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to 51Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy. Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm2 vs 5.8±2.1 pmol/cm2) (p
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Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces. Methods: Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to 51Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy. Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm2 vs 5.8±2.1 pmol/cm2) (p&lt;0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin). Conclusions: Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2006.113688</identifier><identifier>PMID: 17272649</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Acids ; Animals ; Biological and medical sciences ; dilated intercellular spaces ; DIS ; Esophagus ; Esophagus - drug effects ; Esophagus - metabolism ; Esophagus - ultrastructure ; Experiments ; Extracellular Space - drug effects ; Gastro-Oesophageal Reflux ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastroesophageal reflux ; gastroesophageal reflux disease ; Gastrointestinal Agents - pharmacology ; GERD ; HPA ; Hydrochloric Acid - pharmacology ; hypothalamic-pituitary-adrenal ; Hypotheses ; KHBB ; Krebs–Henseleit bicarbonate buffer ; Male ; Mast Cells - cytology ; Medical sciences ; Microscopy, Electron - methods ; Models, Animal ; Mucous Membrane - drug effects ; Mucous Membrane - metabolism ; Mucous Membrane - ultrastructure ; oesophageal mucosa ; Other diseases. Semiology ; Partial Restraint Stress ; Pathogenesis ; Pepsin A - pharmacology ; Performance evaluation ; Permeability ; PRS ; rat ; Rats ; Rats, Sprague-Dawley ; Rodents ; stress ; Stress, Psychological - metabolism ; Studies ; TEM ; transmission electron microscopy</subject><ispartof>Gut, 2007-09, Vol.56 (9), p.1191-1197</ispartof><rights>Copyright 2007 by Gut</rights><rights>2007 INIST-CNRS</rights><rights>Copyright: 2007 Copyright 2007 by Gut</rights><rights>Copyright © 2007 BMJ Publishing Group &amp; British Society of Gastroenterology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b588t-ab09a271320390e95e3f47ae553ef89bdbb54c06d9b9746a2de80f336d4851a03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954970/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954970/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18964715$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17272649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farré, Ricard</creatorcontrib><creatorcontrib>De Vos, Rita</creatorcontrib><creatorcontrib>Geboes, Karel</creatorcontrib><creatorcontrib>Verbecke, Kristine</creatorcontrib><creatorcontrib>Berghe, Pieter Vanden</creatorcontrib><creatorcontrib>Depoortere, Inge</creatorcontrib><creatorcontrib>Blondeau, Kathleen</creatorcontrib><creatorcontrib>Tack, Jan</creatorcontrib><creatorcontrib>Sifrim, Daniel</creatorcontrib><title>Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces</title><title>Gut</title><addtitle>Gut</addtitle><description>Background: In patients with non-erosive gastroesophageal reflux disease, heartburn can occur when acid reaches sensory nerve endings through oesophageal-mucosa-dilated intercellular spaces. Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces. Methods: Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to 51Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy. Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm2 vs 5.8±2.1 pmol/cm2) (p&lt;0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin). Conclusions: Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.</description><subject>Acids</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>dilated intercellular spaces</subject><subject>DIS</subject><subject>Esophagus</subject><subject>Esophagus - drug effects</subject><subject>Esophagus - metabolism</subject><subject>Esophagus - ultrastructure</subject><subject>Experiments</subject><subject>Extracellular Space - drug effects</subject><subject>Gastro-Oesophageal Reflux</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gastroesophageal reflux</subject><subject>gastroesophageal reflux disease</subject><subject>Gastrointestinal Agents - pharmacology</subject><subject>GERD</subject><subject>HPA</subject><subject>Hydrochloric Acid - pharmacology</subject><subject>hypothalamic-pituitary-adrenal</subject><subject>Hypotheses</subject><subject>KHBB</subject><subject>Krebs–Henseleit bicarbonate buffer</subject><subject>Male</subject><subject>Mast Cells - cytology</subject><subject>Medical sciences</subject><subject>Microscopy, Electron - methods</subject><subject>Models, Animal</subject><subject>Mucous Membrane - drug effects</subject><subject>Mucous Membrane - metabolism</subject><subject>Mucous Membrane - ultrastructure</subject><subject>oesophageal mucosa</subject><subject>Other diseases. Semiology</subject><subject>Partial Restraint Stress</subject><subject>Pathogenesis</subject><subject>Pepsin A - pharmacology</subject><subject>Performance evaluation</subject><subject>Permeability</subject><subject>PRS</subject><subject>rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>stress</subject><subject>Stress, Psychological - metabolism</subject><subject>Studies</subject><subject>TEM</subject><subject>transmission electron microscopy</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqF0d-L1DAQB_Agird3-uybFMR7EHqXNM2vlwNd_MmiCCqHL2HaTveytk1NWvH-e7N2uVNfhEAI88kww5eQR4yeMcbl-XaezgpK5e-X1nfIipVS57zQ-i5ZUcpULlRpjshxjDtKqdaG3SdHTBWqkKVZEVwHN7kauiz4DjPfZnEKGGPmhnTqgBCxyTxGP17BFpPr59pHyEYMPULlOjddZzA0WeM6mJJ1w4Shxq6bOwhZHKHG-IDca6GL-PBwn5DPr15-Wr_JNx9ev10_3-SV0HrKoaIGCsV4QbmhaATytlSAQnBstamaqhJlTWVjKqNKCUWDmracy6bUggHlJ-Ri6TvOVY9NjcMUoLNjcD2Ea-vB2b8rg7uyW__DMiNKo_YNTg8Ngv8-Y5xs7-J-GRjQz9FKzSSnkiX45B-483MY0nKWKWU411LqpM4XVQcfY8D2ZhRG7T4ymwK0-wDtEmD68fjPDW79IbEEnh4AxBRbG2CoXbx12shSMZFcvjgXJ_x5U4fwzUrFlbDvv6ytUJt3X19cXtqPyT9bfNXv_jvlL6Zawkg</recordid><startdate>20070901</startdate><enddate>20070901</enddate><creator>Farré, Ricard</creator><creator>De Vos, Rita</creator><creator>Geboes, Karel</creator><creator>Verbecke, Kristine</creator><creator>Berghe, Pieter Vanden</creator><creator>Depoortere, Inge</creator><creator>Blondeau, Kathleen</creator><creator>Tack, Jan</creator><creator>Sifrim, Daniel</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070901</creationdate><title>Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces</title><author>Farré, Ricard ; De Vos, Rita ; Geboes, Karel ; Verbecke, Kristine ; Berghe, Pieter Vanden ; Depoortere, Inge ; Blondeau, Kathleen ; Tack, Jan ; Sifrim, Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b588t-ab09a271320390e95e3f47ae553ef89bdbb54c06d9b9746a2de80f336d4851a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>dilated intercellular spaces</topic><topic>DIS</topic><topic>Esophagus</topic><topic>Esophagus - drug effects</topic><topic>Esophagus - metabolism</topic><topic>Esophagus - ultrastructure</topic><topic>Experiments</topic><topic>Extracellular Space - drug effects</topic><topic>Gastro-Oesophageal Reflux</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gastroesophageal reflux</topic><topic>gastroesophageal reflux disease</topic><topic>Gastrointestinal Agents - pharmacology</topic><topic>GERD</topic><topic>HPA</topic><topic>Hydrochloric Acid - pharmacology</topic><topic>hypothalamic-pituitary-adrenal</topic><topic>Hypotheses</topic><topic>KHBB</topic><topic>Krebs–Henseleit bicarbonate buffer</topic><topic>Male</topic><topic>Mast Cells - cytology</topic><topic>Medical sciences</topic><topic>Microscopy, Electron - methods</topic><topic>Models, Animal</topic><topic>Mucous Membrane - drug effects</topic><topic>Mucous Membrane - metabolism</topic><topic>Mucous Membrane - ultrastructure</topic><topic>oesophageal mucosa</topic><topic>Other diseases. 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Stressful life events may increase heartburn perception. In the rat, acute stress increases gastric and intestinal mucosa permeability. We investigated whether acute stress can also increase oesophageal mucosa permeability and contribute to the dilation of mucosa intercellular spaces. Methods: Male Sprague–Dawley rats were submitted to partial restraint stress. Oesophageal mucosa from stressed and control rats was mounted in diffusion chambers. The permeability to 51Cr-EDTA (400 Da), fluorescein isothiocyanate (FITC)-dextran 4000 Da (FD4) and FITC-dextran 20 000 Da (FD20) was assessed after tissue incubation either with Krebs (control) or HCl pH 2.0+ pepsin 1 mg/ml. The diameter of intercellular spaces was assessed using transmission electron microscopy. Results: Acute stress increased faecal output, small-intestinal permeability and glycaemia. Exposure of oesophageal mucosa from control rats to acid-pepsin did not increase permeability to any of the tested molecules. Stress increased the number of submucosal mast cells and, by itself, increased the permeability to the smallest molecule (22.8±7.1 pmol/cm2 vs 5.8±2.1 pmol/cm2) (p&lt;0.001). Exposure of mucosa from stressed rats to acid-pepsin significantly increased permeability to all molecules tested. Electron microscopy showed dilated intercellular spaces only in mucosa from stressed rats (with and without exposure to acid-pepsin). Conclusions: Acute stress can increase, by itself, oesophageal mucosa permeability. There is a potentiation between stress and exposure of the oesophageal mucosa to acid-pepsin, leading to increased permeability and dilated intercellular spaces.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><pmid>17272649</pmid><doi>10.1136/gut.2006.113688</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Acids
Animals
Biological and medical sciences
dilated intercellular spaces
DIS
Esophagus
Esophagus - drug effects
Esophagus - metabolism
Esophagus - ultrastructure
Experiments
Extracellular Space - drug effects
Gastro-Oesophageal Reflux
Gastroenterology. Liver. Pancreas. Abdomen
Gastroesophageal reflux
gastroesophageal reflux disease
Gastrointestinal Agents - pharmacology
GERD
HPA
Hydrochloric Acid - pharmacology
hypothalamic-pituitary-adrenal
Hypotheses
KHBB
Krebs–Henseleit bicarbonate buffer
Male
Mast Cells - cytology
Medical sciences
Microscopy, Electron - methods
Models, Animal
Mucous Membrane - drug effects
Mucous Membrane - metabolism
Mucous Membrane - ultrastructure
oesophageal mucosa
Other diseases. Semiology
Partial Restraint Stress
Pathogenesis
Pepsin A - pharmacology
Performance evaluation
Permeability
PRS
rat
Rats
Rats, Sprague-Dawley
Rodents
stress
Stress, Psychological - metabolism
Studies
TEM
transmission electron microscopy
title Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces
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