5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro
5‐Hydroxytryptamine (5‐HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be...
Gespeichert in:
| Veröffentlicht in: | British journal of pharmacology 2002-03, Vol.135 (5), p.1144-1151 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1151 |
|---|---|
| container_issue | 5 |
| container_start_page | 1144 |
| container_title | British journal of pharmacology |
| container_volume | 135 |
| creator | Borman, R A Tilford, N S Harmer, D W Day, N Ellis, E S Sheldrick, R L G Carey, J Coleman, R A Baxter, G S |
| description | 5‐Hydroxytryptamine (5‐HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5‐HT2B receptors in human colon, and to establish their possible role in the aetiology of IBS.
The distribution of 5‐HT2B receptor mRNA and protein were investigated by quantitative RT – PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5‐HT2B receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5‐HT2B receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers.
Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally‐mediated contractile responses, that were significantly potentiated by application of 5‐HT (up to 10−7 M), with a pEC50 of 8.2±0.1 (n=49 donors). The response to 5‐HT was inhibited by a number of selective 5‐HT2B receptor antagonists.
This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5‐HT in human colon are mediated by 5‐HT2B receptors. It is proposed that these receptors contribute to the putative 5‐HT‐induced colonic smooth muscle hypersensitivity associated with IBS.
British Journal of Pharmacology (2002) 135, 1144–1151; doi:10.1038/sj.bjp.0704571 |
| doi_str_mv | 10.1038/sj.bjp.0704571 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1573235</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1024119761</sourcerecordid><originalsourceid>FETCH-LOGICAL-j4153-12c866ffc97670dba34e5a812a54f0b42d36dd34265dd1490c7c3afe960198623</originalsourceid><addsrcrecordid>eNpVkc1u1DAUhS1URIfCtmurUpcZfP2bbCrRqjBIlWBR1pbHsTtOM3GwM22z4xF4Rp4Ej2YEYmVdn0_nHt2D0DmQJRBWf8jdct2NS6IIFwpeoQVwJSvBajhBC0KIqgDq-hS9zbkjpIhKvEGn5U8pRskCbcTvn79W9_QaJ2fdOMWU8dibGRv86GacYu9wGPDWtcFMYXjA08Zh92LDZAo7Y-e9s1PG0eOD057e7LZmwDb2cdiPT2FK8R167U2f3fvje4a-f7q9v1lVd18_f7n5eFd1HASrgNpaSu9to6Qi7dow7oSpgRrBPVlz2jLZtoxTKdoWeEOsssx410gCTS0pO0NXB99xty6prRumZHo9prA1adbRBP2_MoSNfohPGkS5CBPF4OJokOKPncuT7uIuDSWzpqCggRr20OURMtma3icz2JD_binBGiq5LBw7cM-hd_M_neh9ezp3urSnj-3p628rTiRjfwCmxI-z</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>217191815</pqid></control><display><type>article</type><title>5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro</title><source>Wiley Free Content</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Borman, R A ; Tilford, N S ; Harmer, D W ; Day, N ; Ellis, E S ; Sheldrick, R L G ; Carey, J ; Coleman, R A ; Baxter, G S</creator><creatorcontrib>Borman, R A ; Tilford, N S ; Harmer, D W ; Day, N ; Ellis, E S ; Sheldrick, R L G ; Carey, J ; Coleman, R A ; Baxter, G S</creatorcontrib><description>5‐Hydroxytryptamine (5‐HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5‐HT2B receptors in human colon, and to establish their possible role in the aetiology of IBS.
The distribution of 5‐HT2B receptor mRNA and protein were investigated by quantitative RT – PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5‐HT2B receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5‐HT2B receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers.
Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally‐mediated contractile responses, that were significantly potentiated by application of 5‐HT (up to 10−7 M), with a pEC50 of 8.2±0.1 (n=49 donors). The response to 5‐HT was inhibited by a number of selective 5‐HT2B receptor antagonists.
This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5‐HT in human colon are mediated by 5‐HT2B receptors. It is proposed that these receptors contribute to the putative 5‐HT‐induced colonic smooth muscle hypersensitivity associated with IBS.
British Journal of Pharmacology (2002) 135, 1144–1151; doi:10.1038/sj.bjp.0704571</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0704571</identifier><identifier>PMID: 11877320</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>5‐HT2B ; 5‐Hydroxytryptamine ; Biological and medical sciences ; human colon ; irritable bowel syndrome ; Medical sciences ; motility disorders</subject><ispartof>British journal of pharmacology, 2002-03, Vol.135 (5), p.1144-1151</ispartof><rights>2002 British Pharmacological Society</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Mar 2002</rights><rights>Copyright 2002, Nature Publishing Group 2002 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573235/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573235/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14992646$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Borman, R A</creatorcontrib><creatorcontrib>Tilford, N S</creatorcontrib><creatorcontrib>Harmer, D W</creatorcontrib><creatorcontrib>Day, N</creatorcontrib><creatorcontrib>Ellis, E S</creatorcontrib><creatorcontrib>Sheldrick, R L G</creatorcontrib><creatorcontrib>Carey, J</creatorcontrib><creatorcontrib>Coleman, R A</creatorcontrib><creatorcontrib>Baxter, G S</creatorcontrib><title>5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro</title><title>British journal of pharmacology</title><description>5‐Hydroxytryptamine (5‐HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5‐HT2B receptors in human colon, and to establish their possible role in the aetiology of IBS.
The distribution of 5‐HT2B receptor mRNA and protein were investigated by quantitative RT – PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5‐HT2B receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5‐HT2B receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers.
Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally‐mediated contractile responses, that were significantly potentiated by application of 5‐HT (up to 10−7 M), with a pEC50 of 8.2±0.1 (n=49 donors). The response to 5‐HT was inhibited by a number of selective 5‐HT2B receptor antagonists.
This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5‐HT in human colon are mediated by 5‐HT2B receptors. It is proposed that these receptors contribute to the putative 5‐HT‐induced colonic smooth muscle hypersensitivity associated with IBS.
British Journal of Pharmacology (2002) 135, 1144–1151; doi:10.1038/sj.bjp.0704571</description><subject>5‐HT2B</subject><subject>5‐Hydroxytryptamine</subject><subject>Biological and medical sciences</subject><subject>human colon</subject><subject>irritable bowel syndrome</subject><subject>Medical sciences</subject><subject>motility disorders</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpVkc1u1DAUhS1URIfCtmurUpcZfP2bbCrRqjBIlWBR1pbHsTtOM3GwM22z4xF4Rp4Ej2YEYmVdn0_nHt2D0DmQJRBWf8jdct2NS6IIFwpeoQVwJSvBajhBC0KIqgDq-hS9zbkjpIhKvEGn5U8pRskCbcTvn79W9_QaJ2fdOMWU8dibGRv86GacYu9wGPDWtcFMYXjA08Zh92LDZAo7Y-e9s1PG0eOD057e7LZmwDb2cdiPT2FK8R167U2f3fvje4a-f7q9v1lVd18_f7n5eFd1HASrgNpaSu9to6Qi7dow7oSpgRrBPVlz2jLZtoxTKdoWeEOsssx410gCTS0pO0NXB99xty6prRumZHo9prA1adbRBP2_MoSNfohPGkS5CBPF4OJokOKPncuT7uIuDSWzpqCggRr20OURMtma3icz2JD_binBGiq5LBw7cM-hd_M_neh9ezp3urSnj-3p628rTiRjfwCmxI-z</recordid><startdate>200203</startdate><enddate>200203</enddate><creator>Borman, R A</creator><creator>Tilford, N S</creator><creator>Harmer, D W</creator><creator>Day, N</creator><creator>Ellis, E S</creator><creator>Sheldrick, R L G</creator><creator>Carey, J</creator><creator>Coleman, R A</creator><creator>Baxter, G S</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</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>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>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>200203</creationdate><title>5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro</title><author>Borman, R A ; Tilford, N S ; Harmer, D W ; Day, N ; Ellis, E S ; Sheldrick, R L G ; Carey, J ; Coleman, R A ; Baxter, G S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j4153-12c866ffc97670dba34e5a812a54f0b42d36dd34265dd1490c7c3afe960198623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>5‐HT2B</topic><topic>5‐Hydroxytryptamine</topic><topic>Biological and medical sciences</topic><topic>human colon</topic><topic>irritable bowel syndrome</topic><topic>Medical sciences</topic><topic>motility disorders</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borman, R A</creatorcontrib><creatorcontrib>Tilford, N S</creatorcontrib><creatorcontrib>Harmer, D W</creatorcontrib><creatorcontrib>Day, N</creatorcontrib><creatorcontrib>Ellis, E S</creatorcontrib><creatorcontrib>Sheldrick, R L G</creatorcontrib><creatorcontrib>Carey, J</creatorcontrib><creatorcontrib>Coleman, R A</creatorcontrib><creatorcontrib>Baxter, G S</creatorcontrib><collection>Pascal-Francis</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences 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>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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Borman, R A</au><au>Tilford, N S</au><au>Harmer, D W</au><au>Day, N</au><au>Ellis, E S</au><au>Sheldrick, R L G</au><au>Carey, J</au><au>Coleman, R A</au><au>Baxter, G S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro</atitle><jtitle>British journal of pharmacology</jtitle><date>2002-03</date><risdate>2002</risdate><volume>135</volume><issue>5</issue><spage>1144</spage><epage>1151</epage><pages>1144-1151</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>5‐Hydroxytryptamine (5‐HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. The aim of the present study was to investigate the distribution and function of 5‐HT2B receptors in human colon, and to establish their possible role in the aetiology of IBS.
The distribution of 5‐HT2B receptor mRNA and protein were investigated by quantitative RT – PCR, Western analysis and immunocytochemistry. High levels of both mRNA and protein for 5‐HT2B receptors were found throughout the human gastrointestinal tract, and in particular in colon, where 5‐HT2B receptors were found predominantly in the longitudinal and circular smooth muscle layers within the muscularis externa, and in the myenteric nerve plexus lying between these two layers.
Electrical field stimulation of longitudinal muscle preparations of human colon mounted in organ baths resulted in neuronally‐mediated contractile responses, that were significantly potentiated by application of 5‐HT (up to 10−7 M), with a pEC50 of 8.2±0.1 (n=49 donors). The response to 5‐HT was inhibited by a number of selective 5‐HT2B receptor antagonists.
This study has shown for the first time that, in contrast to animal studies, the excitatory effects of 5‐HT in human colon are mediated by 5‐HT2B receptors. It is proposed that these receptors contribute to the putative 5‐HT‐induced colonic smooth muscle hypersensitivity associated with IBS.
British Journal of Pharmacology (2002) 135, 1144–1151; doi:10.1038/sj.bjp.0704571</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11877320</pmid><doi>10.1038/sj.bjp.0704571</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1188 |
| ispartof | British journal of pharmacology, 2002-03, Vol.135 (5), p.1144-1151 |
| issn | 0007-1188 1476-5381 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1573235 |
| source | Wiley Free Content; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | 5‐HT2B 5‐Hydroxytryptamine Biological and medical sciences human colon irritable bowel syndrome Medical sciences motility disorders |
| title | 5‐HT2B receptors play a key role in mediating the excitatory effects of 5‐HT in human colon in vitro |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T04%3A46%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=5%E2%80%90HT2B%20receptors%20play%20a%20key%20role%20in%20mediating%20the%20excitatory%20effects%20of%205%E2%80%90HT%20in%20human%20colon%20in%20vitro&rft.jtitle=British%20journal%20of%20pharmacology&rft.au=Borman,%20R%20A&rft.date=2002-03&rft.volume=135&rft.issue=5&rft.spage=1144&rft.epage=1151&rft.pages=1144-1151&rft.issn=0007-1188&rft.eissn=1476-5381&rft.coden=BJPCBM&rft_id=info:doi/10.1038/sj.bjp.0704571&rft_dat=%3Cproquest_pubme%3E1024119761%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=217191815&rft_id=info:pmid/11877320&rfr_iscdi=true |