Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801
Identifieur interne : 001988 ( Istex/Corpus ); précédent : 001987; suivant : 001989Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801
Auteurs : Lionel Bert ; Daniel Rodier ; Isabelle Bougault ; Nathalie Allouard ; Gérard Le-Fur ; Philippe Soubrié ; Régis SteinbergSource :
- Synapse [ 0887-4476 ] ; 2002-01.
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Abstract
The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.
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DOI: 10.1002/syn.10021
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ISTEX:FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38ALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title><author><name sortKey="Bert, Lionel" sort="Bert, Lionel" uniqKey="Bert L" first="Lionel" last="Bert">Lionel Bert</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, UCBL, Faculté de Pharmacie, 8, av. 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Rockefeller, 69373 LYON Cedex 08, France</mods:affiliation></affiliation></author><author><name sortKey="Rodier, Daniel" sort="Rodier, Daniel" uniqKey="Rodier D" first="Daniel" last="Rodier">Daniel Rodier</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation></author><author><name sortKey="Bougault, Isabelle" sort="Bougault, Isabelle" uniqKey="Bougault I" first="Isabelle" last="Bougault">Isabelle Bougault</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation></author><author><name sortKey="Allouard, Nathalie" sort="Allouard, Nathalie" uniqKey="Allouard N" first="Nathalie" last="Allouard">Nathalie Allouard</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation></author><author><name sortKey="Le Ur, Gerard" sort="Le Ur, Gerard" uniqKey="Le Ur G" first="Gérard" last="Le-Fur">Gérard Le-Fur</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation></author><author><name sortKey="Soubrie, Philippe" sort="Soubrie, Philippe" uniqKey="Soubrie P" first="Philippe" last="Soubrié">Philippe Soubrié</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation></author><author><name sortKey="Steinberg, Regis" sort="Steinberg, Regis" uniqKey="Steinberg R" first="Régis" last="Steinberg">Régis Steinberg</name><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Sanofi‐Synthélabo, Central Nervous System Department, 371, rue du Prof. Blayac, 34184 Montpellier Cedex 04, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2002-01">2002-01</date><biblScope unit="volume">43</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="62">62</biblScope><biblScope unit="page" to="69">69</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A</idno><idno type="DOI">10.1002/syn.10021</idno><idno type="ArticleID">SYN10021</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>dual probe microdialysis</term><term>guinea pig</term><term>norepinephrine</term><term>prefrontal cortex</term><term>tachykinin antagonists</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Lionel Bert</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string><json:string>Current Address: Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, UCBL, Faculté de Pharmacie, 8, av. Rockefeller, 69373 LYON Cedex 08, France</json:string></affiliations></json:item><json:item><name>Daniel Rodier</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string></affiliations></json:item><json:item><name>Isabelle Bougault</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string></affiliations></json:item><json:item><name>Nathalie Allouard</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string></affiliations></json:item><json:item><name>Gérard Le‐Fur</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string></affiliations></json:item><json:item><name>Philippe Soubrié</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string></affiliations></json:item><json:item><name>Régis Steinberg</name><affiliations><json:string>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</json:string><json:string>Sanofi‐Synthélabo, Central Nervous System Department, 371, rue du Prof. Blayac, 34184 Montpellier Cedex 04, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>tachykinin antagonists</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dual probe microdialysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>guinea pig</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>norepinephrine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>prefrontal cortex</value></json:item></subject><articleId><json:string>SYN10021</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. 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medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>2002</publicationDate><copyrightDate>2002</copyrightDate><doi><json:string>10.1002/syn.10021</json:string></doi><id>FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A</id><score>0.19438958</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><availability><p>Copyright © 2001 Wiley‐Liss, Inc.</p></availability><date>2002</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title><author xml:id="author-1"><persName><forename type="first">Lionel</forename><surname>Bert</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><affiliation>Current Address: Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, UCBL, Faculté de Pharmacie, 8, av. Rockefeller, 69373 LYON Cedex 08, France</affiliation></author><author xml:id="author-2"><persName><forename type="first">Daniel</forename><surname>Rodier</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation></author><author xml:id="author-3"><persName><forename type="first">Isabelle</forename><surname>Bougault</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Nathalie</forename><surname>Allouard</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">Gérard</forename><surname>Le‐Fur</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Philippe</forename><surname>Soubrié</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Régis</forename><surname>Steinberg</surname></persName><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, 371, rue du Prof. Blayac, 34184 Montpellier Cedex 04, France</affiliation></author></analytic><monogr><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="pISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><idno type="DOI">10.1002/(ISSN)1098-2396</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2002-01"></date><biblScope unit="volume">43</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="62">62</biblScope><biblScope unit="page" to="69">69</biblScope></imprint></monogr><idno type="istex">FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A</idno><idno type="DOI">10.1002/syn.10021</idno><idno type="ArticleID">SYN10021</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2002</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>tachykinin antagonists</term></item><item><term>dual probe microdialysis</term></item><item><term>guinea pig</term></item><item><term>norepinephrine</term></item><item><term>prefrontal cortex</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001-04-30">Received</change><change when="2001-08-28">Registration</change><change when="2002-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>John Wiley & Sons, Inc.</publisherName><publisherLoc>New York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1098-2396</doi><issn type="print">0887-4476</issn><issn type="electronic">1098-2396</issn><idGroup><id type="product" value="SYN"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="SYNAPSE">Synapse</title><title type="short">Synapse</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley" registered="yes">10.1002/syn.v43:1</doi><numberingGroup><numbering type="journalVolume" number="43">43</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2002-01">January 2002</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="70" status="forIssue"><doi origin="wiley" registered="yes">10.1002/syn.10021</doi><idGroup><id type="unit" value="SYN10021"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><copyright ownership="publisher">Copyright © 2001 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2001-04-30"></event><event type="manuscriptAccepted" date="2001-08-28"></event><event type="firstOnline" date="2001-10-30"></event><event type="publishedOnlineFinalForm" date="2001-10-30"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-04"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-10"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-11-03"></event></eventGroup><numberingGroup><numbering type="pageFirst">62</numbering><numbering type="pageLast">69</numbering></numberingGroup><correspondenceTo>Sanofi‐Synthélabo, Central Nervous System Department, 371, rue du Prof. Blayac, 34184 Montpellier Cedex 04, France</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:SYN.SYN10021.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="5"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="48"></count><count type="wordTotal" number="6461"></count></countGroup><titleGroup><title type="main" xml:lang="en">Permissive role of neurokinin NK<sub>3</sub> receptors in NK<sub>1</sub> receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title><title type="short" xml:lang="en">NK<sub>3</sub> Control of NK<sub>1</sub> Agonist‐Induced NE Release</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" currentRef="#curr1"><personName><givenNames>Lionel</givenNames><familyName>Bert</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Daniel</givenNames><familyName>Rodier</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Isabelle</givenNames><familyName>Bougault</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Nathalie</givenNames><familyName>Allouard</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Gérard</givenNames><familyName>Le‐Fur</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Philippe</givenNames><familyName>Soubrié</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Régis</givenNames><familyName>Steinberg</familyName></personName><contactDetails><email normalForm="regis.steinberg@sanofi-synthelabo.com">regis.steinberg@sanofi‐synthelabo.com</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</unparsedAffiliation></affiliation><affiliation xml:id="curr1" countryCode="FR"><unparsedAffiliation>Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, UCBL, Faculté de Pharmacie, 8, av. Rockefeller, 69373 LYON Cedex 08, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">tachykinin antagonists</keyword><keyword xml:id="kwd2">dual probe microdialysis</keyword><keyword xml:id="kwd3">guinea pig</keyword><keyword xml:id="kwd4">norepinephrine</keyword><keyword xml:id="kwd5">prefrontal cortex</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The present experiments investigated the role of neurokinin‐1 (NK<sub>1</sub>) and neurokinin‐3 (NK<sub>3</sub>) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK<sub>1</sub> receptor agonists [SAR<sup>9</sup>,Met(O<sub>2</sub>)<sup>11</sup>]‐SP (10 μM) and septide (1 μM) as well as the selective NK<sub>3</sub> receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR<sup>9</sup>,Met(O<sub>2</sub>)<sup>11</sup>]‐SP was completely blocked by the peripheral administration of the selective non peptide NK<sub>1</sub> and NK<sub>3</sub> receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR<sup>9</sup>,Met(O<sub>2</sub>)<sup>11</sup>]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR<sup>9</sup>,Met(O<sub>2</sub>)<sup>11</sup>]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10<sup>−9</sup> M). These results demonstrate that stimulation of NK<sub>1</sub> and NK<sub>3</sub> receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK<sub>1</sub> receptor agonists require NKB/NK<sub>3</sub> receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>NK3 Control of NK1 Agonist‐Induced NE Release</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Permissive role of neurokinin NK3 receptors in NK1 receptor‐mediated activation of the locus coeruleus revealed by SR 142801</title></titleInfo><name type="personal"><namePart type="given">Lionel</namePart><namePart type="family">Bert</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><affiliation>Current Address: Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, UCBL, Faculté de Pharmacie, 8, av. Rockefeller, 69373 LYON Cedex 08, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Daniel</namePart><namePart type="family">Rodier</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Isabelle</namePart><namePart type="family">Bougault</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nathalie</namePart><namePart type="family">Allouard</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gérard</namePart><namePart type="family">Le‐Fur</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philippe</namePart><namePart type="family">Soubrié</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Régis</namePart><namePart type="family">Steinberg</namePart><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, Montpellier, France</affiliation><affiliation>Sanofi‐Synthélabo, Central Nervous System Department, 371, rue du Prof. Blayac, 34184 Montpellier Cedex 04, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2002-01</dateIssued><dateCaptured encoding="w3cdtf">2001-04-30</dateCaptured><dateValid encoding="w3cdtf">2001-08-28</dateValid><copyrightDate encoding="w3cdtf">2002</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">5</extent><extent unit="references">48</extent><extent unit="words">6461</extent></physicalDescription><abstract lang="en">The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.</abstract><subject lang="en"><genre>keywords</genre><topic>tachykinin antagonists</topic><topic>dual probe microdialysis</topic><topic>guinea pig</topic><topic>norepinephrine</topic><topic>prefrontal cortex</topic></subject><relatedItem type="host"><titleInfo><title>Synapse</title></titleInfo><titleInfo type="abbreviated"><title>Synapse</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0887-4476</identifier><identifier type="eISSN">1098-2396</identifier><identifier type="DOI">10.1002/(ISSN)1098-2396</identifier><identifier type="PublisherID">SYN</identifier><part><date>2002</date><detail type="volume"><caption>vol.</caption><number>43</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>62</start><end>69</end><total>8</total></extent></part></relatedItem><identifier type="istex">FEF08F0BC4EDFB435E530D688DE2B5B4C9E7C38A</identifier><identifier type="DOI">10.1002/syn.10021</identifier><identifier type="ArticleID">SYN10021</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2001 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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