Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations
It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT -receptors. Therefore, we studied transgenic mice that only express the human 5-HT receptor in cardiomyocytes in the atrium and in the ventricle (5-HT -TG), their wild type-littermates (WT) and isolated human at...
Gespeichert in:
Veröffentlicht in: | European journal of pharmacology 2021-06, Vol.901, p.174074 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | |
container_start_page | 174074 |
container_title | European journal of pharmacology |
container_volume | 901 |
creator | Neumann, Joachim Seidler, Tom Fehse, Charlotte Marušáková, Margaréta Hofmann, Britt Gergs, Ulrich |
description | It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT
-receptors. Therefore, we studied transgenic mice that only express the human 5-HT
receptor in cardiomyocytes in the atrium and in the ventricle (5-HT
-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC
= 6.0 ± 0.1; n = 7) from 5-HT
-TG, isolated spontaneously beating right atrial preparations (pEC
= 6.1 ± 0.1; n = 7) from 5-HT
-TG, Langendorff perfused hearts from 5-HT
-TG, living 5-HT
-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT
-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT
-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT
-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT
-TG dextrally, resp., to higher concentrations: the pEC
of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 μM metoclopramide (n = 5; P |
doi_str_mv | 10.1016/j.ejphar.2021.174074 |
format | Article |
fullrecord | <record><control><sourceid>pubmed</sourceid><recordid>TN_cdi_pubmed_primary_33811834</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33811834</sourcerecordid><originalsourceid>FETCH-pubmed_primary_338118343</originalsourceid><addsrcrecordid>eNqFj0lOw0AQRVtIiIThBgjVBWy6PWBnHYFygOyjortMynIPqm4jcQxuzAKyZvU37z3pK_VodG20eXmea5rTGaVudGNqM3R66K7U1ozDrtKDaTbqNudZa93vmv5Gbdp2NGZsu6363qM4jp-Y7bqgAE0T2ZIhTuCpRLvEJOjZEWBw4KJPJOxiIIgBzqvHAH11OEIHVSaJJQYOlZClVKJk4ABFMOQPCmzBs_3t8MXFIowLJKGEgoVjyPfqesIl08Pf3qmnt9fj_lCl9d2TOyVhj_J1unxo_wV-AMKSW60</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations</title><source>Elsevier ScienceDirect Journals</source><creator>Neumann, Joachim ; Seidler, Tom ; Fehse, Charlotte ; Marušáková, Margaréta ; Hofmann, Britt ; Gergs, Ulrich</creator><creatorcontrib>Neumann, Joachim ; Seidler, Tom ; Fehse, Charlotte ; Marušáková, Margaréta ; Hofmann, Britt ; Gergs, Ulrich</creatorcontrib><description>It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT
-receptors. Therefore, we studied transgenic mice that only express the human 5-HT
receptor in cardiomyocytes in the atrium and in the ventricle (5-HT
-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC
= 6.0 ± 0.1; n = 7) from 5-HT
-TG, isolated spontaneously beating right atrial preparations (pEC
= 6.1 ± 0.1; n = 7) from 5-HT
-TG, Langendorff perfused hearts from 5-HT
-TG, living 5-HT
-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT
-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT
-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT
-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT
-TG dextrally, resp., to higher concentrations: the pEC
of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 μM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 μM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT
receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT
-receptors.</description><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2021.174074</identifier><identifier>PMID: 33811834</identifier><language>eng</language><publisher>Netherlands</publisher><ispartof>European journal of pharmacology, 2021-06, Vol.901, p.174074</ispartof><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></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/33811834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Neumann, Joachim</creatorcontrib><creatorcontrib>Seidler, Tom</creatorcontrib><creatorcontrib>Fehse, Charlotte</creatorcontrib><creatorcontrib>Marušáková, Margaréta</creatorcontrib><creatorcontrib>Hofmann, Britt</creatorcontrib><creatorcontrib>Gergs, Ulrich</creatorcontrib><title>Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT
-receptors. Therefore, we studied transgenic mice that only express the human 5-HT
receptor in cardiomyocytes in the atrium and in the ventricle (5-HT
-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC
= 6.0 ± 0.1; n = 7) from 5-HT
-TG, isolated spontaneously beating right atrial preparations (pEC
= 6.1 ± 0.1; n = 7) from 5-HT
-TG, Langendorff perfused hearts from 5-HT
-TG, living 5-HT
-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT
-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT
-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT
-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT
-TG dextrally, resp., to higher concentrations: the pEC
of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 μM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 μM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT
receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT
-receptors.</description><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFj0lOw0AQRVtIiIThBgjVBWy6PWBnHYFygOyjortMynIPqm4jcQxuzAKyZvU37z3pK_VodG20eXmea5rTGaVudGNqM3R66K7U1ozDrtKDaTbqNudZa93vmv5Gbdp2NGZsu6363qM4jp-Y7bqgAE0T2ZIhTuCpRLvEJOjZEWBw4KJPJOxiIIgBzqvHAH11OEIHVSaJJQYOlZClVKJk4ABFMOQPCmzBs_3t8MXFIowLJKGEgoVjyPfqesIl08Pf3qmnt9fj_lCl9d2TOyVhj_J1unxo_wV-AMKSW60</recordid><startdate>20210615</startdate><enddate>20210615</enddate><creator>Neumann, Joachim</creator><creator>Seidler, Tom</creator><creator>Fehse, Charlotte</creator><creator>Marušáková, Margaréta</creator><creator>Hofmann, Britt</creator><creator>Gergs, Ulrich</creator><scope>NPM</scope></search><sort><creationdate>20210615</creationdate><title>Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations</title><author>Neumann, Joachim ; Seidler, Tom ; Fehse, Charlotte ; Marušáková, Margaréta ; Hofmann, Britt ; Gergs, Ulrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_338118343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Neumann, Joachim</creatorcontrib><creatorcontrib>Seidler, Tom</creatorcontrib><creatorcontrib>Fehse, Charlotte</creatorcontrib><creatorcontrib>Marušáková, Margaréta</creatorcontrib><creatorcontrib>Hofmann, Britt</creatorcontrib><creatorcontrib>Gergs, Ulrich</creatorcontrib><collection>PubMed</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Neumann, Joachim</au><au>Seidler, Tom</au><au>Fehse, Charlotte</au><au>Marušáková, Margaréta</au><au>Hofmann, Britt</au><au>Gergs, Ulrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2021-06-15</date><risdate>2021</risdate><volume>901</volume><spage>174074</spage><pages>174074-</pages><eissn>1879-0712</eissn><abstract>It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT
-receptors. Therefore, we studied transgenic mice that only express the human 5-HT
receptor in cardiomyocytes in the atrium and in the ventricle (5-HT
-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC
= 6.0 ± 0.1; n = 7) from 5-HT
-TG, isolated spontaneously beating right atrial preparations (pEC
= 6.1 ± 0.1; n = 7) from 5-HT
-TG, Langendorff perfused hearts from 5-HT
-TG, living 5-HT
-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT
-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT
-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT
-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT
-TG dextrally, resp., to higher concentrations: the pEC
of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 μM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 μM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT
receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT
-receptors.</abstract><cop>Netherlands</cop><pmid>33811834</pmid><doi>10.1016/j.ejphar.2021.174074</doi></addata></record> |
fulltext | fulltext |
identifier | EISSN: 1879-0712 |
ispartof | European journal of pharmacology, 2021-06, Vol.901, p.174074 |
issn | 1879-0712 |
language | eng |
recordid | cdi_pubmed_primary_33811834 |
source | Elsevier ScienceDirect Journals |
title | Cardiovascular effects of metoclopramide and domperidone on human 5-HT 4 -serotonin-receptors in transgenic mice and in human atrial preparations |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T18%3A40%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cardiovascular%20effects%20of%20metoclopramide%20and%20domperidone%20on%20human%205-HT%204%20-serotonin-receptors%20in%20transgenic%20mice%20and%20in%20human%20atrial%20preparations&rft.jtitle=European%20journal%20of%20pharmacology&rft.au=Neumann,%20Joachim&rft.date=2021-06-15&rft.volume=901&rft.spage=174074&rft.pages=174074-&rft.eissn=1879-0712&rft_id=info:doi/10.1016/j.ejphar.2021.174074&rft_dat=%3Cpubmed%3E33811834%3C/pubmed%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33811834&rfr_iscdi=true |