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Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle
cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was an...
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Published in: | European journal of pharmacology 2011-11, Vol.670 (1), p.266-271 |
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creator | Ertl, Claudia Lukowski, Robert Sigl, Katja Schlossmann, Jens Hofmann, Franz Wegener, Jörg W. |
description | cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI−/− mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles. |
doi_str_mv | 10.1016/j.ejphar.2011.07.048 |
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Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI−/− mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2011.07.048</identifier><identifier>PMID: 21914444</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Biological and medical sciences ; cGMP ; Cyclic GMP - analogs & derivatives ; Cyclic GMP - metabolism ; Cyclic GMP - pharmacology ; Electric Stimulation ; Female ; Fundus ; Gastric Fundus ; Gene Expression Regulation - drug effects ; In Vitro Techniques ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinetics ; Male ; Medical sciences ; Mice ; Muscle Relaxation - drug effects ; Muscle, Smooth - cytology ; Muscle, Smooth - drug effects ; Muscle, Smooth - metabolism ; Muscle, Smooth - physiology ; NANC ; Neurons - drug effects ; Neurons - metabolism ; Nitric oxide ; Pharmacology. Drug treatments ; Protein Isoforms - metabolism ; Relaxation ; Signal Transduction - drug effects</subject><ispartof>European journal of pharmacology, 2011-11, Vol.670 (1), p.266-271</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-a1d01cab99a3f8b99d0873de8508822826f938db080942852c56192ad15d29af3</citedby><cites>FETCH-LOGICAL-c391t-a1d01cab99a3f8b99d0873de8508822826f938db080942852c56192ad15d29af3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24637814$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21914444$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ertl, Claudia</creatorcontrib><creatorcontrib>Lukowski, Robert</creatorcontrib><creatorcontrib>Sigl, Katja</creatorcontrib><creatorcontrib>Schlossmann, Jens</creatorcontrib><creatorcontrib>Hofmann, Franz</creatorcontrib><creatorcontrib>Wegener, Jörg W.</creatorcontrib><title>Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI−/− mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>cGMP</subject><subject>Cyclic GMP - analogs & derivatives</subject><subject>Cyclic GMP - metabolism</subject><subject>Cyclic GMP - pharmacology</subject><subject>Electric Stimulation</subject><subject>Female</subject><subject>Fundus</subject><subject>Gastric Fundus</subject><subject>Gene Expression Regulation - drug effects</subject><subject>In Vitro Techniques</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Muscle Relaxation - drug effects</subject><subject>Muscle, Smooth - cytology</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth - metabolism</subject><subject>Muscle, Smooth - physiology</subject><subject>NANC</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Nitric oxide</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Isoforms - metabolism</subject><subject>Relaxation</subject><subject>Signal Transduction - drug effects</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9kD1PwzAQhi0EgvLxDxDygpgS7pyksRckVEFBFMEAs-XaDrhKnGIniP57UrXAxi23PO97p4eQU4QUAceXi9Qulu8qpAwQUyhTyPkOGSEvRQIlsl0yAsA8YUKIA3IY4wIACsGKfXLAUGA-zIjcPDhvO6cjbSsabK2-VOdaT-crqqePz5d6-nBPo3vzqnb-jTpPq96bPtLYtG33Tps-6toek71K1dGebPcReb29eZncJbOn6f3kepboTGCXKDSAWs2FUFnFh2WAl5mxvADOGeNsXImMmzlwEDnjBdPFGAVTBgvDhKqyI3Kx6V2G9qO3sZONi9rWtfK27aPkYqjKMYeBzDekDm2MwVZyGVyjwkoiyLU_uZAbf3LtT0IpB39D7Gx7oJ831vyGfoQNwPkWUFGrugrKaxf_uHyclRzX3NWGs4OOT2eDjNpZr61xwepOmtb9_8k3yneOPg</recordid><startdate>20111116</startdate><enddate>20111116</enddate><creator>Ertl, Claudia</creator><creator>Lukowski, Robert</creator><creator>Sigl, Katja</creator><creator>Schlossmann, Jens</creator><creator>Hofmann, Franz</creator><creator>Wegener, Jörg W.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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>20111116</creationdate><title>Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle</title><author>Ertl, Claudia ; Lukowski, Robert ; Sigl, Katja ; Schlossmann, Jens ; Hofmann, Franz ; Wegener, Jörg W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-a1d01cab99a3f8b99d0873de8508822826f938db080942852c56192ad15d29af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>cGMP</topic><topic>Cyclic GMP - analogs & derivatives</topic><topic>Cyclic GMP - metabolism</topic><topic>Cyclic GMP - pharmacology</topic><topic>Electric Stimulation</topic><topic>Female</topic><topic>Fundus</topic><topic>Gastric Fundus</topic><topic>Gene Expression Regulation - drug effects</topic><topic>In Vitro Techniques</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Muscle Relaxation - drug effects</topic><topic>Muscle, Smooth - cytology</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth - metabolism</topic><topic>Muscle, Smooth - physiology</topic><topic>NANC</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Nitric oxide</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Isoforms - metabolism</topic><topic>Relaxation</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ertl, Claudia</creatorcontrib><creatorcontrib>Lukowski, Robert</creatorcontrib><creatorcontrib>Sigl, Katja</creatorcontrib><creatorcontrib>Schlossmann, Jens</creatorcontrib><creatorcontrib>Hofmann, Franz</creatorcontrib><creatorcontrib>Wegener, Jörg W.</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>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ertl, Claudia</au><au>Lukowski, Robert</au><au>Sigl, Katja</au><au>Schlossmann, Jens</au><au>Hofmann, Franz</au><au>Wegener, Jörg W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2011-11-16</date><risdate>2011</risdate><volume>670</volume><issue>1</issue><spage>266</spage><epage>271</epage><pages>266-271</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI−/− mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21914444</pmid><doi>10.1016/j.ejphar.2011.07.048</doi><tpages>6</tpages></addata></record> |
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subjects | Animals Biological and medical sciences cGMP Cyclic GMP - analogs & derivatives Cyclic GMP - metabolism Cyclic GMP - pharmacology Electric Stimulation Female Fundus Gastric Fundus Gene Expression Regulation - drug effects In Vitro Techniques Intracellular Signaling Peptides and Proteins - metabolism Kinetics Male Medical sciences Mice Muscle Relaxation - drug effects Muscle, Smooth - cytology Muscle, Smooth - drug effects Muscle, Smooth - metabolism Muscle, Smooth - physiology NANC Neurons - drug effects Neurons - metabolism Nitric oxide Pharmacology. Drug treatments Protein Isoforms - metabolism Relaxation Signal Transduction - drug effects |
title | Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle |
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