Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice
Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in pri...
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description | Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice. |
doi_str_mv | 10.1038/labinvest.2012.14 |
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Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2012.14</identifier><identifier>PMID: 22330338</identifier><identifier>CODEN: LAINAW</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>631/250/249/2510/9 ; 692/420 ; 692/699/1503/1581/257 ; Animals ; Biological and medical sciences ; Biotechnology ; Carbolines - pharmacology ; Dextran Sulfate - administration & dosage ; Dextran Sulfate - adverse effects ; Disease Models, Animal ; Electromyography ; enteric nervous system ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Hyperalgesia - metabolism ; Hyperalgesia - physiopathology ; inflammatory bowel disease ; Inflammatory Bowel Diseases - chemically induced ; Inflammatory Bowel Diseases - metabolism ; Inflammatory Bowel Diseases - physiopathology ; Intestinal Mucosa - innervation ; Intestinal Mucosa - metabolism ; Investigative techniques, diagnostic techniques (general aspects) ; Laboratory Medicine ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Nociception - drug effects ; Other diseases. Semiology ; Pathology ; Pyrazines - pharmacology ; Pyridines - pharmacology ; Receptors, Serotonin, 5-HT3 - metabolism ; Receptors, Serotonin, 5-HT4 - metabolism ; research-article ; serotonin ; Serotonin - metabolism ; Serotonin Antagonists - pharmacology ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Time Factors ; TRPV Cation Channels - analysis ; TRPV Cation Channels - antagonists & inhibitors ; TRPV Cation Channels - metabolism ; TRPV1 ; Tryptophan Hydroxylase - metabolism ; Visceral Afferents - metabolism ; Visceral Afferents - physiopathology ; visceral hypersensitivity</subject><ispartof>Laboratory investigation, 2012-05, Vol.92 (5), p.769-782</ispartof><rights>2012 United States & Canadian Academy of Pathology</rights><rights>United States and Canadian Academy of Pathology, Inc. 2012</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group May 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-9cc52798481d959946ddbbdd447e0c581d0584cd6b30dd96ae7f44e4b71dc01f3</citedby><cites>FETCH-LOGICAL-c596t-9cc52798481d959946ddbbdd447e0c581d0584cd6b30dd96ae7f44e4b71dc01f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25918634$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22330338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsumoto, Kenjiro</creatorcontrib><creatorcontrib>Lo, Mee Wah</creatorcontrib><creatorcontrib>Hosoya, Takuji</creatorcontrib><creatorcontrib>Tashima, Kimihito</creatorcontrib><creatorcontrib>Takayama, Hiromitsu</creatorcontrib><creatorcontrib>Murayama, Toshihiko</creatorcontrib><creatorcontrib>Horie, Syunji</creatorcontrib><title>Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice.</description><subject>631/250/249/2510/9</subject><subject>692/420</subject><subject>692/699/1503/1581/257</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Carbolines - pharmacology</subject><subject>Dextran Sulfate - administration & dosage</subject><subject>Dextran Sulfate - adverse effects</subject><subject>Disease Models, Animal</subject><subject>Electromyography</subject><subject>enteric nervous system</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hyperalgesia - metabolism</subject><subject>Hyperalgesia - physiopathology</subject><subject>inflammatory bowel disease</subject><subject>Inflammatory Bowel Diseases - chemically induced</subject><subject>Inflammatory Bowel Diseases - metabolism</subject><subject>Inflammatory Bowel Diseases - physiopathology</subject><subject>Intestinal Mucosa - innervation</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Confocal</subject><subject>Nociception - drug effects</subject><subject>Other diseases. Semiology</subject><subject>Pathology</subject><subject>Pyrazines - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Receptors, Serotonin, 5-HT3 - metabolism</subject><subject>Receptors, Serotonin, 5-HT4 - metabolism</subject><subject>research-article</subject><subject>serotonin</subject><subject>Serotonin - metabolism</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hyperalgesia - metabolism</topic><topic>Hyperalgesia - physiopathology</topic><topic>inflammatory bowel disease</topic><topic>Inflammatory Bowel Diseases - chemically induced</topic><topic>Inflammatory Bowel Diseases - metabolism</topic><topic>Inflammatory Bowel Diseases - physiopathology</topic><topic>Intestinal Mucosa - innervation</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Confocal</topic><topic>Nociception - drug effects</topic><topic>Other diseases. Semiology</topic><topic>Pathology</topic><topic>Pyrazines - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Receptors, Serotonin, 5-HT3 - metabolism</topic><topic>Receptors, Serotonin, 5-HT4 - metabolism</topic><topic>research-article</topic><topic>serotonin</topic><topic>Serotonin - metabolism</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Time Factors</topic><topic>TRPV Cation Channels - analysis</topic><topic>TRPV Cation Channels - antagonists & inhibitors</topic><topic>TRPV Cation Channels - metabolism</topic><topic>TRPV1</topic><topic>Tryptophan Hydroxylase - metabolism</topic><topic>Visceral Afferents - metabolism</topic><topic>Visceral Afferents - physiopathology</topic><topic>visceral hypersensitivity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsumoto, Kenjiro</creatorcontrib><creatorcontrib>Lo, Mee Wah</creatorcontrib><creatorcontrib>Hosoya, Takuji</creatorcontrib><creatorcontrib>Tashima, Kimihito</creatorcontrib><creatorcontrib>Takayama, Hiromitsu</creatorcontrib><creatorcontrib>Murayama, Toshihiko</creatorcontrib><creatorcontrib>Horie, Syunji</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsumoto, Kenjiro</au><au>Lo, Mee Wah</au><au>Hosoya, Takuji</au><au>Tashima, Kimihito</au><au>Takayama, Hiromitsu</au><au>Murayama, Toshihiko</au><au>Horie, Syunji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>92</volume><issue>5</issue><spage>769</spage><epage>782</epage><pages>769-782</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><coden>LAINAW</coden><abstract>Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>22330338</pmid><doi>10.1038/labinvest.2012.14</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/250/249/2510/9 692/420 692/699/1503/1581/257 Animals Biological and medical sciences Biotechnology Carbolines - pharmacology Dextran Sulfate - administration & dosage Dextran Sulfate - adverse effects Disease Models, Animal Electromyography enteric nervous system Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Hyperalgesia - metabolism Hyperalgesia - physiopathology inflammatory bowel disease Inflammatory Bowel Diseases - chemically induced Inflammatory Bowel Diseases - metabolism Inflammatory Bowel Diseases - physiopathology Intestinal Mucosa - innervation Intestinal Mucosa - metabolism Investigative techniques, diagnostic techniques (general aspects) Laboratory Medicine Male Medical sciences Medicine Medicine & Public Health Mice Mice, Inbred C57BL Microscopy, Confocal Nociception - drug effects Other diseases. Semiology Pathology Pyrazines - pharmacology Pyridines - pharmacology Receptors, Serotonin, 5-HT3 - metabolism Receptors, Serotonin, 5-HT4 - metabolism research-article serotonin Serotonin - metabolism Serotonin Antagonists - pharmacology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Time Factors TRPV Cation Channels - analysis TRPV Cation Channels - antagonists & inhibitors TRPV Cation Channels - metabolism TRPV1 Tryptophan Hydroxylase - metabolism Visceral Afferents - metabolism Visceral Afferents - physiopathology visceral hypersensitivity |
title | Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice |
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