A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats
RS-127445 is a selective, high affinity 5-HT(2B)receptor antagonist. We investigated whether 5-HT(2B)receptor antagonists can reduce colonic visceral hypersensitivity caused by restraint stress or by proximal colonic inflammation. Visceral hypersensitivity was induced in rats by either restraint str...
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| Veröffentlicht in: | Neurogastroenterology and motility 2010-02, Vol.22 (2), p.e69-e76 |
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| creator | Ohashi-Doi, K Himaki, D Nagao, K Kawai, M Gale, J D Furness, J B Kurebayashi, Y |
| description | RS-127445 is a selective, high affinity 5-HT(2B)receptor antagonist. We investigated whether 5-HT(2B)receptor antagonists can reduce colonic visceral hypersensitivity caused by restraint stress or by proximal colonic inflammation.
Visceral hypersensitivity was induced in rats by either restraint stress or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon. Restraint stress produced a significant increase in numbers of abdominal contractions evoked by colorectal distension (CRD), measured as a quantitative index of visceral nociception in rats. Seven days after TNBS injection, the pain threshold to CRD at the non-inflamed distal colon, that was determined as the minimum pressure required to evoke abdominal cramp, was significantly decreased. The effect of RS-127445 on visceral hypersensitivity was assessed in either naïve or TNBS-treated rats.
Oral administration of a selective, high affinity 5-HT(2B)receptor antagonist, RS-127445, significantly inhibited visceral hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg kg(-1)). Oral RS-127445 produced a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg(-1)), although it was without significant effect on the visceral nociceptive threshold of naïve rats. RS-127445 (1 to 30 mg kg(-1), p.o.) also dose-dependently reduced the restraint stress-induced defecation in naïve and TNBS-treated rats.
These results suggest that 5-HT(2B)receptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity. |
| doi_str_mv | 10.1111/j.1365-2982.2009.01395.x |
| format | Article |
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Visceral hypersensitivity was induced in rats by either restraint stress or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon. Restraint stress produced a significant increase in numbers of abdominal contractions evoked by colorectal distension (CRD), measured as a quantitative index of visceral nociception in rats. Seven days after TNBS injection, the pain threshold to CRD at the non-inflamed distal colon, that was determined as the minimum pressure required to evoke abdominal cramp, was significantly decreased. The effect of RS-127445 on visceral hypersensitivity was assessed in either naïve or TNBS-treated rats.
Oral administration of a selective, high affinity 5-HT(2B)receptor antagonist, RS-127445, significantly inhibited visceral hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg kg(-1)). Oral RS-127445 produced a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg(-1)), although it was without significant effect on the visceral nociceptive threshold of naïve rats. RS-127445 (1 to 30 mg kg(-1), p.o.) also dose-dependently reduced the restraint stress-induced defecation in naïve and TNBS-treated rats.
These results suggest that 5-HT(2B)receptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity.</description><identifier>ISSN: 1350-1925</identifier><identifier>EISSN: 1365-2982</identifier><identifier>DOI: 10.1111/j.1365-2982.2009.01395.x</identifier><identifier>PMID: 19740115</identifier><language>eng</language><publisher>England</publisher><subject>Analysis of Variance ; Animals ; Colon - drug effects ; Colon - pathology ; Colon - physiopathology ; Dose-Response Relationship, Drug ; Hypersensitivity - drug therapy ; Hypersensitivity - physiopathology ; Indoles - pharmacology ; Inflammation - pathology ; Inflammation - physiopathology ; Male ; Muscle Contraction - drug effects ; Muscle Contraction - physiology ; Muscle, Smooth - drug effects ; Muscle, Smooth - physiopathology ; Pain Measurement ; Pain Threshold - drug effects ; Pain Threshold - physiology ; Pyrimidines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2B - physiology ; Restraint, Physical ; Serotonin 5-HT2 Receptor Antagonists ; Statistics, Nonparametric ; Stress, Physiological - physiology ; Trinitrobenzenesulfonic Acid - toxicity ; Urea - analogs & derivatives ; Urea - pharmacology</subject><ispartof>Neurogastroenterology and motility, 2010-02, Vol.22 (2), p.e69-e76</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1595-aef62476e7c97f16a2d8d78ff0aa8d68620e01bb896b627bd6ffb3e2df68628c3</citedby><cites>FETCH-LOGICAL-c1595-aef62476e7c97f16a2d8d78ff0aa8d68620e01bb896b627bd6ffb3e2df68628c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19740115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohashi-Doi, K</creatorcontrib><creatorcontrib>Himaki, D</creatorcontrib><creatorcontrib>Nagao, K</creatorcontrib><creatorcontrib>Kawai, M</creatorcontrib><creatorcontrib>Gale, J D</creatorcontrib><creatorcontrib>Furness, J B</creatorcontrib><creatorcontrib>Kurebayashi, Y</creatorcontrib><title>A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats</title><title>Neurogastroenterology and motility</title><addtitle>Neurogastroenterol Motil</addtitle><description>RS-127445 is a selective, high affinity 5-HT(2B)receptor antagonist. We investigated whether 5-HT(2B)receptor antagonists can reduce colonic visceral hypersensitivity caused by restraint stress or by proximal colonic inflammation.
Visceral hypersensitivity was induced in rats by either restraint stress or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon. Restraint stress produced a significant increase in numbers of abdominal contractions evoked by colorectal distension (CRD), measured as a quantitative index of visceral nociception in rats. Seven days after TNBS injection, the pain threshold to CRD at the non-inflamed distal colon, that was determined as the minimum pressure required to evoke abdominal cramp, was significantly decreased. The effect of RS-127445 on visceral hypersensitivity was assessed in either naïve or TNBS-treated rats.
Oral administration of a selective, high affinity 5-HT(2B)receptor antagonist, RS-127445, significantly inhibited visceral hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg kg(-1)). Oral RS-127445 produced a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg(-1)), although it was without significant effect on the visceral nociceptive threshold of naïve rats. RS-127445 (1 to 30 mg kg(-1), p.o.) also dose-dependently reduced the restraint stress-induced defecation in naïve and TNBS-treated rats.
These results suggest that 5-HT(2B)receptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Colon - drug effects</subject><subject>Colon - pathology</subject><subject>Colon - physiopathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hypersensitivity - drug therapy</subject><subject>Hypersensitivity - physiopathology</subject><subject>Indoles - pharmacology</subject><subject>Inflammation - pathology</subject><subject>Inflammation - physiopathology</subject><subject>Male</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle Contraction - physiology</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - physiopathology</subject><subject>Pain Measurement</subject><subject>Pain Threshold - drug effects</subject><subject>Pain Threshold - physiology</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Serotonin, 5-HT2B - physiology</subject><subject>Restraint, Physical</subject><subject>Serotonin 5-HT2 Receptor Antagonists</subject><subject>Statistics, Nonparametric</subject><subject>Stress, Physiological - physiology</subject><subject>Trinitrobenzenesulfonic Acid - toxicity</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - pharmacology</subject><issn>1350-1925</issn><issn>1365-2982</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFOwzAMhiMEYmPwCig3LrQk6ZKmx4GAIU3iMs5R2jprpq4dSTZtb0_DJvDBtmT_v60PIUxJSod4Wqc0EzxhhWQpI6RICc0Knh4u0PhvcBl7ThJaMD5CN96vCSGCTcU1GtEinxJK-RjpGfbQQhXsHh5xY1cN1sbYzoYj5sl8idkzdlDBNvQO6y7oVd9ZH7DtGlva4PHe-gqcbnFz3ILz0Hk7eEW57bDTwd-iK6NbD3fnOkFfb6_Ll3my-Hz_eJktkorygicazPBcLiCvitxQoVkt61waQ7SWtZCCESC0LGUhSsHyshbGlBmw2sSZrLIJejj5bl3_vQMf1Ca-1ra6g37nVZ5lgtIhDZvytFm53nsHRm2d3Wh3VJSoyFetVcSoIkYV-apfvuowSO_PR3blBup_4Rlo9gMjd3gO</recordid><startdate>201002</startdate><enddate>201002</enddate><creator>Ohashi-Doi, K</creator><creator>Himaki, D</creator><creator>Nagao, K</creator><creator>Kawai, M</creator><creator>Gale, J D</creator><creator>Furness, J B</creator><creator>Kurebayashi, Y</creator><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>7X8</scope></search><sort><creationdate>201002</creationdate><title>A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats</title><author>Ohashi-Doi, K ; Himaki, D ; Nagao, K ; Kawai, M ; Gale, J D ; Furness, J B ; Kurebayashi, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1595-aef62476e7c97f16a2d8d78ff0aa8d68620e01bb896b627bd6ffb3e2df68628c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Colon - drug effects</topic><topic>Colon - pathology</topic><topic>Colon - physiopathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hypersensitivity - drug therapy</topic><topic>Hypersensitivity - physiopathology</topic><topic>Indoles - pharmacology</topic><topic>Inflammation - pathology</topic><topic>Inflammation - physiopathology</topic><topic>Male</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle Contraction - physiology</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - physiopathology</topic><topic>Pain Measurement</topic><topic>Pain Threshold - drug effects</topic><topic>Pain Threshold - physiology</topic><topic>Pyrimidines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Serotonin, 5-HT2B - physiology</topic><topic>Restraint, Physical</topic><topic>Serotonin 5-HT2 Receptor Antagonists</topic><topic>Statistics, Nonparametric</topic><topic>Stress, Physiological - physiology</topic><topic>Trinitrobenzenesulfonic Acid - toxicity</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohashi-Doi, K</creatorcontrib><creatorcontrib>Himaki, D</creatorcontrib><creatorcontrib>Nagao, K</creatorcontrib><creatorcontrib>Kawai, M</creatorcontrib><creatorcontrib>Gale, J D</creatorcontrib><creatorcontrib>Furness, J B</creatorcontrib><creatorcontrib>Kurebayashi, Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neurogastroenterology and motility</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohashi-Doi, K</au><au>Himaki, D</au><au>Nagao, K</au><au>Kawai, M</au><au>Gale, J D</au><au>Furness, J B</au><au>Kurebayashi, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats</atitle><jtitle>Neurogastroenterology and motility</jtitle><addtitle>Neurogastroenterol Motil</addtitle><date>2010-02</date><risdate>2010</risdate><volume>22</volume><issue>2</issue><spage>e69</spage><epage>e76</epage><pages>e69-e76</pages><issn>1350-1925</issn><eissn>1365-2982</eissn><abstract>RS-127445 is a selective, high affinity 5-HT(2B)receptor antagonist. We investigated whether 5-HT(2B)receptor antagonists can reduce colonic visceral hypersensitivity caused by restraint stress or by proximal colonic inflammation.
Visceral hypersensitivity was induced in rats by either restraint stress or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon. Restraint stress produced a significant increase in numbers of abdominal contractions evoked by colorectal distension (CRD), measured as a quantitative index of visceral nociception in rats. Seven days after TNBS injection, the pain threshold to CRD at the non-inflamed distal colon, that was determined as the minimum pressure required to evoke abdominal cramp, was significantly decreased. The effect of RS-127445 on visceral hypersensitivity was assessed in either naïve or TNBS-treated rats.
Oral administration of a selective, high affinity 5-HT(2B)receptor antagonist, RS-127445, significantly inhibited visceral hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg kg(-1)). Oral RS-127445 produced a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg(-1)), although it was without significant effect on the visceral nociceptive threshold of naïve rats. RS-127445 (1 to 30 mg kg(-1), p.o.) also dose-dependently reduced the restraint stress-induced defecation in naïve and TNBS-treated rats.
These results suggest that 5-HT(2B)receptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT(2B)receptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity.</abstract><cop>England</cop><pmid>19740115</pmid><doi>10.1111/j.1365-2982.2009.01395.x</doi></addata></record> |
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| subjects | Analysis of Variance Animals Colon - drug effects Colon - pathology Colon - physiopathology Dose-Response Relationship, Drug Hypersensitivity - drug therapy Hypersensitivity - physiopathology Indoles - pharmacology Inflammation - pathology Inflammation - physiopathology Male Muscle Contraction - drug effects Muscle Contraction - physiology Muscle, Smooth - drug effects Muscle, Smooth - physiopathology Pain Measurement Pain Threshold - drug effects Pain Threshold - physiology Pyrimidines - pharmacology Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT2B - physiology Restraint, Physical Serotonin 5-HT2 Receptor Antagonists Statistics, Nonparametric Stress, Physiological - physiology Trinitrobenzenesulfonic Acid - toxicity Urea - analogs & derivatives Urea - pharmacology |
| title | A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats |
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