Mechanisms of transforming growth factor-α (TGF-α) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins
The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted r...
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Veröffentlicht in: | Digestive diseases and sciences 2003-02, Vol.48 (2), p.329-333 |
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description | The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation. |
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The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1023/A:1021935728607</identifier><identifier>PMID: 12643611</identifier><identifier>CODEN: DDSCDJ</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Alcoholism and acute alcohol poisoning ; Analysis of Variance ; Animals ; Biological and medical sciences ; Calcitonin Gene-Related Peptide - analysis ; Capsaicin - pharmacology ; Disease Models, Animal ; Ethanol ; Gastric Mucosa - drug effects ; Gastric Mucosa - pathology ; Gastritis - prevention & control ; Indomethacin - pharmacology ; Injections, Intraperitoneal ; Male ; Medical sciences ; Neurons, Afferent ; Neuropeptides - analysis ; Probability ; Prostaglandins - analysis ; Radionuclide Imaging ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Sensitivity and Specificity ; Stomach - diagnostic imaging ; Stomach - drug effects ; Substance P - analysis ; Toxicology ; Transforming Growth Factor alpha - pharmacology</subject><ispartof>Digestive diseases and sciences, 2003-02, Vol.48 (2), p.329-333</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c283t-1d5161bddacda8bad8cc4a664c93d1c2d3774174fbfeed1f6aede1b34139ebac3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14546112$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12643611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VONGTHAVARAVAT, Verapan</creatorcontrib><creatorcontrib>MESIYA, Sikandar</creatorcontrib><creatorcontrib>SAYMEH, Layth</creatorcontrib><creatorcontrib>YANG XIA</creatorcontrib><creatorcontrib>HARTY, Richard F</creatorcontrib><title>Mechanisms of transforming growth factor-α (TGF-α) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><description>The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.</description><subject>Alcoholism and acute alcohol poisoning</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcitonin Gene-Related Peptide - analysis</subject><subject>Capsaicin - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Ethanol</subject><subject>Gastric Mucosa - drug effects</subject><subject>Gastric Mucosa - pathology</subject><subject>Gastritis - prevention & control</subject><subject>Indomethacin - pharmacology</subject><subject>Injections, Intraperitoneal</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurons, Afferent</subject><subject>Neuropeptides - analysis</subject><subject>Probability</subject><subject>Prostaglandins - analysis</subject><subject>Radionuclide Imaging</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reference Values</subject><subject>Sensitivity and Specificity</subject><subject>Stomach - diagnostic imaging</subject><subject>Stomach - drug effects</subject><subject>Substance P - analysis</subject><subject>Toxicology</subject><subject>Transforming Growth Factor alpha - pharmacology</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEFrFEEQhZugJGvMOTfpi0HB0anpmZ7Z3EIwUYgEJJ6Xmu6a2ZaZ7rWrh5Af5SF_JL_JRlfES71H8fFeUUKcQvkeykp9uDjPAmvVtFWny_ZArKBpVVE1unsmViXo7AH0kXjB_L0sy3UL-lAcQaVrpQFW4ucXMlv0jmeWYZApouchxNn5UY4x3KetHNCkEIunR_nm7voq61vpvF0MWTkipxh2MSQyyQUvcUTnOUlKOTRMGZRpSzJiOpdfw0S_S5g8h_ggPS0xeH73_2JHu-Qs5TV6K3M2Jxyn7HPwS_F8wInpZK_H4tvVx7vLT8XN7fXny4ubwlSdSgXYBjT01qKx2PVoO2Nq1Lo2a2XBVFa1bQ1tPfQDkYVBI1mCXtWg1tSjUcfi7E9urv-xEKfN7NjQlM-gsPCmVQBlHhl8tQeXfia72UU3Y3zY_H1wBl7vAWSD05D_axz_4-qmzlilfgGeaZED</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>VONGTHAVARAVAT, Verapan</creator><creator>MESIYA, Sikandar</creator><creator>SAYMEH, Layth</creator><creator>YANG XIA</creator><creator>HARTY, Richard F</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>Mechanisms of transforming growth factor-α (TGF-α) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins</title><author>VONGTHAVARAVAT, Verapan ; MESIYA, Sikandar ; SAYMEH, Layth ; YANG XIA ; HARTY, Richard F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c283t-1d5161bddacda8bad8cc4a664c93d1c2d3774174fbfeed1f6aede1b34139ebac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Alcoholism and acute alcohol poisoning</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcitonin Gene-Related Peptide - analysis</topic><topic>Capsaicin - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Ethanol</topic><topic>Gastric Mucosa - drug effects</topic><topic>Gastric Mucosa - pathology</topic><topic>Gastritis - prevention & control</topic><topic>Indomethacin - pharmacology</topic><topic>Injections, Intraperitoneal</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurons, Afferent</topic><topic>Neuropeptides - analysis</topic><topic>Probability</topic><topic>Prostaglandins - analysis</topic><topic>Radionuclide Imaging</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reference Values</topic><topic>Sensitivity and Specificity</topic><topic>Stomach - diagnostic imaging</topic><topic>Stomach - drug effects</topic><topic>Substance P - analysis</topic><topic>Toxicology</topic><topic>Transforming Growth Factor alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VONGTHAVARAVAT, Verapan</creatorcontrib><creatorcontrib>MESIYA, Sikandar</creatorcontrib><creatorcontrib>SAYMEH, Layth</creatorcontrib><creatorcontrib>YANG XIA</creatorcontrib><creatorcontrib>HARTY, Richard F</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VONGTHAVARAVAT, Verapan</au><au>MESIYA, Sikandar</au><au>SAYMEH, Layth</au><au>YANG XIA</au><au>HARTY, Richard F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of transforming growth factor-α (TGF-α) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins</atitle><jtitle>Digestive diseases and sciences</jtitle><addtitle>Dig Dis Sci</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>48</volume><issue>2</issue><spage>329</spage><epage>333</epage><pages>329-333</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><coden>DDSCDJ</coden><abstract>The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.</abstract><cop>Heidelberg</cop><pub>Springer</pub><pmid>12643611</pmid><doi>10.1023/A:1021935728607</doi><tpages>5</tpages></addata></record> |
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subjects | Alcoholism and acute alcohol poisoning Analysis of Variance Animals Biological and medical sciences Calcitonin Gene-Related Peptide - analysis Capsaicin - pharmacology Disease Models, Animal Ethanol Gastric Mucosa - drug effects Gastric Mucosa - pathology Gastritis - prevention & control Indomethacin - pharmacology Injections, Intraperitoneal Male Medical sciences Neurons, Afferent Neuropeptides - analysis Probability Prostaglandins - analysis Radionuclide Imaging Random Allocation Rats Rats, Sprague-Dawley Reference Values Sensitivity and Specificity Stomach - diagnostic imaging Stomach - drug effects Substance P - analysis Toxicology Transforming Growth Factor alpha - pharmacology |
title | Mechanisms of transforming growth factor-α (TGF-α) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins |
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