Demonstration of functional M3‐muscarinic receptors in ventricular cardiomyocytes of adult rats
Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M2‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M2‐receptor. For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced...
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| description | Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M2‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M2‐receptor.
For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [3H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists.
Carbachol (10−7–10−3 mol l−1) increased IP‐formation (maximal increase: 14±3% above basal, n=6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml−1 for 20 h): maximal increase was 31±5%, pEC50‐value was 5.08±0.33 (n=6).
In PTX‐pretreated cardiomyocytes 100 μmol l−1 carbachol‐induced IP‐formation was inhibited by atropine (pKi‐value: 8.89±0.10) and by the M3‐receptor antagonist darifenacin (pKi‐value: 8.67±0.23) but was not significantly affected by the M1‐receptor antagonist pirenzepine (1 μmol l−1) or the M2‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l−1).
In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M2‐receptor, that is coupled to activation of the phospholipase C/IP3‐pathway; this receptor is very likely of the M3‐subtype.
British Journal of Pharmacology (2003) 138, 156–160. doi:10.1038/sj.bjp.0704997 |
| doi_str_mv | 10.1038/sj.bjp.0704997 |
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For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [3H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists.
Carbachol (10−7–10−3 mol l−1) increased IP‐formation (maximal increase: 14±3% above basal, n=6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml−1 for 20 h): maximal increase was 31±5%, pEC50‐value was 5.08±0.33 (n=6).
In PTX‐pretreated cardiomyocytes 100 μmol l−1 carbachol‐induced IP‐formation was inhibited by atropine (pKi‐value: 8.89±0.10) and by the M3‐receptor antagonist darifenacin (pKi‐value: 8.67±0.23) but was not significantly affected by the M1‐receptor antagonist pirenzepine (1 μmol l−1) or the M2‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l−1).
In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M2‐receptor, that is coupled to activation of the phospholipase C/IP3‐pathway; this receptor is very likely of the M3‐subtype.
British Journal of Pharmacology (2003) 138, 156–160. doi:10.1038/sj.bjp.0704997</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0704997</identifier><identifier>PMID: 12522085</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aging - physiology ; Animals ; Biological and medical sciences ; carbachol ; Cell receptors ; Cell structures and functions ; darifenacin ; Dose-Response Relationship, Drug ; Fundamental and applied biological sciences. Psychology ; Heart Ventricles - cytology ; Heart Ventricles - drug effects ; Heart Ventricles - metabolism ; inositol phosphates ; Inositol Phosphates - metabolism ; M2‐receptors ; M3‐receptors ; Male ; Molecular and cellular biology ; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - physiology ; pertussis toxin ; Rat cardiomyocytes ; Rats ; Rats, Wistar ; Receptor, Muscarinic M3 ; Receptors, Muscarinic - physiology</subject><ispartof>British journal of pharmacology, 2003-01, Vol.138 (1), p.156-160</ispartof><rights>2003 British Pharmacological Society</rights><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jan 2003</rights><rights>Copyright 2003, Nature Publishing Group 2003 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/PMC1573625/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573625/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,4010,27900,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14603621$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12522085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pönicke, Klaus</creatorcontrib><creatorcontrib>Heinroth‐Hoffmann, Ingrid</creatorcontrib><creatorcontrib>Brodde, Otto‐Erich</creatorcontrib><title>Demonstration of functional M3‐muscarinic receptors in ventricular cardiomyocytes of adult rats</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M2‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M2‐receptor.
For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [3H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists.
Carbachol (10−7–10−3 mol l−1) increased IP‐formation (maximal increase: 14±3% above basal, n=6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml−1 for 20 h): maximal increase was 31±5%, pEC50‐value was 5.08±0.33 (n=6).
In PTX‐pretreated cardiomyocytes 100 μmol l−1 carbachol‐induced IP‐formation was inhibited by atropine (pKi‐value: 8.89±0.10) and by the M3‐receptor antagonist darifenacin (pKi‐value: 8.67±0.23) but was not significantly affected by the M1‐receptor antagonist pirenzepine (1 μmol l−1) or the M2‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l−1).
In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M2‐receptor, that is coupled to activation of the phospholipase C/IP3‐pathway; this receptor is very likely of the M3‐subtype.
British Journal of Pharmacology (2003) 138, 156–160. doi:10.1038/sj.bjp.0704997</description><subject>Aging - physiology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>carbachol</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>darifenacin</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - metabolism</subject><subject>inositol phosphates</subject><subject>Inositol Phosphates - metabolism</subject><subject>M2‐receptors</subject><subject>M3‐receptors</subject><subject>Male</subject><subject>Molecular and cellular biology</subject><subject>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - physiology</subject><subject>pertussis toxin</subject><subject>Rat cardiomyocytes</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Muscarinic M3</subject><subject>Receptors, Muscarinic - physiology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkc1u1TAUhC1ERS-FLUsUIcEuF__EsbNBKuWnSEWw6N6ynWNw5MQXOym6Ox6BZ-RJ6qi3LbDykebTeDSD0DOCtwQz-ToPWzPstljgpuvEA7QhjWhrziR5iDYYY1ETIuUxepzzgHERBX-EjgnllGLJN0i_gzFOeU569nGqoqvcMtn11qH6zP78-j0u2erkJ2-rBBZ2c0y58lN1BdOcvF2CTlUBeh_HfbT7GfLqovslzFVxzU_QkdMhw9PDe4IuP7y_PDuvL758_HR2elEPjLS8ppQYBq6HnnUOLBecCOsMccBl09K2MxYMl9xa0IYZSvuG9E1rnOQgOWcn6M2N7W4xI_R2TaeD2iU_6rRXUXv1rzL57-pbvFKEC9bS1eDVwSDFHwvkWY0-WwhBTxCXrATtOJUtKeCL_8AhLqn0lRUlgsiukbJAz_-Oc5fjtvkCvDwAuvQbXNKT9fmea1pcYq2_sRvupw-wv9exWvdXeVBlf3XYX739et6QjrNrHJanbg</recordid><startdate>200301</startdate><enddate>200301</enddate><creator>Pönicke, Klaus</creator><creator>Heinroth‐Hoffmann, Ingrid</creator><creator>Brodde, Otto‐Erich</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>200301</creationdate><title>Demonstration of functional M3‐muscarinic receptors in ventricular cardiomyocytes of adult rats</title><author>Pönicke, Klaus ; Heinroth‐Hoffmann, Ingrid ; Brodde, Otto‐Erich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j3165-221b3efded39fec57517cfb1fe5846269bceb585cceab3b22d41d46bf85e8553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aging - physiology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>carbachol</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>darifenacin</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - drug effects</topic><topic>Heart Ventricles - metabolism</topic><topic>inositol phosphates</topic><topic>Inositol Phosphates - metabolism</topic><topic>M2‐receptors</topic><topic>M3‐receptors</topic><topic>Male</topic><topic>Molecular and cellular biology</topic><topic>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - physiology</topic><topic>pertussis toxin</topic><topic>Rat cardiomyocytes</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Muscarinic M3</topic><topic>Receptors, Muscarinic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pönicke, Klaus</creatorcontrib><creatorcontrib>Heinroth‐Hoffmann, Ingrid</creatorcontrib><creatorcontrib>Brodde, Otto‐Erich</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>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>MEDLINE - Academic</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>Pönicke, Klaus</au><au>Heinroth‐Hoffmann, Ingrid</au><au>Brodde, Otto‐Erich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Demonstration of functional M3‐muscarinic receptors in ventricular cardiomyocytes of adult rats</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2003-01</date><risdate>2003</risdate><volume>138</volume><issue>1</issue><spage>156</spage><epage>160</epage><pages>156-160</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>Muscarinic receptors (M‐receptors) in the mammalian heart are predominantly of the M2‐subtype. The aim of this study was to find out whether there might exist an additional myocardial non‐M2‐receptor.
For this purpose, we assessed, in adult rat isolated ventricular cardiomyocytes, carbachol‐induced [3H]‐inositol phosphate (IP) formation, and its inhibition by M‐receptor antagonists.
Carbachol (10−7–10−3 mol l−1) increased IP‐formation (maximal increase: 14±3% above basal, n=6). This increase was significantly enhanced by pretreatment with pertussis toxin (PTX, 250 ng ml−1 for 20 h): maximal increase was 31±5%, pEC50‐value was 5.08±0.33 (n=6).
In PTX‐pretreated cardiomyocytes 100 μmol l−1 carbachol‐induced IP‐formation was inhibited by atropine (pKi‐value: 8.89±0.10) and by the M3‐receptor antagonist darifenacin (pKi‐value: 8.67±0.23) but was not significantly affected by the M1‐receptor antagonist pirenzepine (1 μmol l−1) or the M2‐receptor antagonists AF‐DX 116 and himbacine (1 μmol l−1).
In conclusion, in adult rat cardiomyocytes there exists an additional, non‐M2‐receptor, that is coupled to activation of the phospholipase C/IP3‐pathway; this receptor is very likely of the M3‐subtype.
British Journal of Pharmacology (2003) 138, 156–160. doi:10.1038/sj.bjp.0704997</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>12522085</pmid><doi>10.1038/sj.bjp.0704997</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aging - physiology Animals Biological and medical sciences carbachol Cell receptors Cell structures and functions darifenacin Dose-Response Relationship, Drug Fundamental and applied biological sciences. Psychology Heart Ventricles - cytology Heart Ventricles - drug effects Heart Ventricles - metabolism inositol phosphates Inositol Phosphates - metabolism M2‐receptors M3‐receptors Male Molecular and cellular biology Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - physiology pertussis toxin Rat cardiomyocytes Rats Rats, Wistar Receptor, Muscarinic M3 Receptors, Muscarinic - physiology |
| title | Demonstration of functional M3‐muscarinic receptors in ventricular cardiomyocytes of adult rats |
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