Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors
In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial my...
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| Veröffentlicht in: | Molecular pharmacology 1992-02, Vol.41 (2), p.346-351 |
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| creator | OUADID, H SEGUIN, J DUMUIS, A BOCKAERT NARGEOT, J |
| description | In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic
cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT
of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated
enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular
perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline.
The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of
5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic
effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and
stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin),
5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride
and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine.
Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the
pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described
for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations
had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent. |
| format | Article |
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cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT
of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated
enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular
perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline.
The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of
5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic
effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and
stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin),
5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride
and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine.
Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the
pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described
for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations
had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>PMID: 1311410</identifier><identifier>CODEN: MOPMA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Animals ; Anura ; Atrial Function ; Biological and medical sciences ; Calcium - metabolism ; Calcium - physiology ; Calcium Channels - drug effects ; Calcium Channels - physiology ; Cardiotonic Agents - pharmacology ; Cells, Cultured ; Cyclic AMP - metabolism ; Cyclic AMP - physiology ; Fundamental and applied biological sciences. Psychology ; Guinea Pigs ; Heart ; Heart - drug effects ; Heart - physiology ; Heart Atria - drug effects ; Humans ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Myocardium - cytology ; Myocardium - metabolism ; Myocardium - ultrastructure ; Rabbits ; Rats ; Receptors, Serotonin - physiology ; Serotonin - pharmacology ; Species Specificity ; Vertebrates: cardiovascular system</subject><ispartof>Molecular pharmacology, 1992-02, Vol.41 (2), p.346-351</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5117786$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1311410$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OUADID, H</creatorcontrib><creatorcontrib>SEGUIN, J</creatorcontrib><creatorcontrib>DUMUIS, A</creatorcontrib><creatorcontrib>BOCKAERT</creatorcontrib><creatorcontrib>NARGEOT, J</creatorcontrib><title>Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic
cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT
of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated
enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular
perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline.
The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of
5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic
effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and
stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin),
5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride
and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine.
Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the
pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described
for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations
had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.</description><subject>Animals</subject><subject>Anura</subject><subject>Atrial Function</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium - physiology</subject><subject>Calcium Channels - drug effects</subject><subject>Calcium Channels - physiology</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea Pigs</subject><subject>Heart</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>Heart Atria - drug effects</subject><subject>Humans</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - ultrastructure</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Receptors, Serotonin - physiology</subject><subject>Serotonin - pharmacology</subject><subject>Species Specificity</subject><subject>Vertebrates: cardiovascular system</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90E1LxDAQBuAiyrqu_gQhB_VWSNK0TY-y-AULHlTwVqbJ7DbSJjVJ1f57K7t4Gpj3YRjeo2TJcs5Syhg7TpaU8iKVVf5-mpyF8EEpE7mki2TBMsYEo8skvKB30VljibHKIwQMREGnzNgTNXqPNs4JacceLIHoDXSkn5ya4gy_DJDYIrH43U1EY1DeNKhJnraT9u5nin4aIvTGoiAeFQ7R-XCenGyhC3hxmKvk7f7udf2Ybp4fnta3m7TlRR5TIUQ1v6sYrzCXhSh1U0KpKym2f3sKzbbJJFVUNcArDUJrXkjFKyo5byRmq-Rmf3fw7nPEEOveBIVdBxbdGOqSS1bJvJrh5QGOTY-6HrzpwU_1oaU5vzrkEOZuth6sMuGf5YyVpSxmdr1nrdm138ZjPbTge1Cuc7upFqzmdSaK7Bco4oBk</recordid><startdate>19920201</startdate><enddate>19920201</enddate><creator>OUADID, H</creator><creator>SEGUIN, J</creator><creator>DUMUIS, A</creator><creator>BOCKAERT</creator><creator>NARGEOT, J</creator><general>American Society for Pharmacology and Experimental Therapeutics</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>19920201</creationdate><title>Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors</title><author>OUADID, H ; SEGUIN, J ; DUMUIS, A ; BOCKAERT ; NARGEOT, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h265t-4449458c129e58647db7a7d984f94580abfb380c0cba29da4dd268c290822b8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Anura</topic><topic>Atrial Function</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium - physiology</topic><topic>Calcium Channels - drug effects</topic><topic>Calcium Channels - physiology</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea Pigs</topic><topic>Heart</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>Heart Atria - drug effects</topic><topic>Humans</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - ultrastructure</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Receptors, Serotonin - physiology</topic><topic>Serotonin - pharmacology</topic><topic>Species Specificity</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OUADID, H</creatorcontrib><creatorcontrib>SEGUIN, J</creatorcontrib><creatorcontrib>DUMUIS, A</creatorcontrib><creatorcontrib>BOCKAERT</creatorcontrib><creatorcontrib>NARGEOT, J</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>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OUADID, H</au><au>SEGUIN, J</au><au>DUMUIS, A</au><au>BOCKAERT</au><au>NARGEOT, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1992-02-01</date><risdate>1992</risdate><volume>41</volume><issue>2</issue><spage>346</spage><epage>351</epage><pages>346-351</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><coden>MOPMA3</coden><abstract>In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic
cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT
of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated
enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular
perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline.
The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of
5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic
effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and
stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin),
5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride
and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine.
Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the
pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described
for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations
had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.</abstract><cop>Bethesda, MD</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>1311410</pmid><tpages>6</tpages></addata></record> |
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| ispartof | Molecular pharmacology, 1992-02, Vol.41 (2), p.346-351 |
| issn | 0026-895X 1521-0111 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72819859 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Anura Atrial Function Biological and medical sciences Calcium - metabolism Calcium - physiology Calcium Channels - drug effects Calcium Channels - physiology Cardiotonic Agents - pharmacology Cells, Cultured Cyclic AMP - metabolism Cyclic AMP - physiology Fundamental and applied biological sciences. Psychology Guinea Pigs Heart Heart - drug effects Heart - physiology Heart Atria - drug effects Humans Membrane Potentials - drug effects Membrane Potentials - physiology Myocardium - cytology Myocardium - metabolism Myocardium - ultrastructure Rabbits Rats Receptors, Serotonin - physiology Serotonin - pharmacology Species Specificity Vertebrates: cardiovascular system |
| title | Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors |
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