BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION
Identifieur interne : 002F66 ( Main/Corpus ); précédent : 002F65; suivant : 002F67BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION
Auteurs : Peter J. Gebicke-Haerter ; Florian Christoffel ; Jens Timmer ; Hinnak Northoff ; Mathias Berger ; Dietrich Van CalkerSource :
- Neurochemistry International [ 0197-0186 ] ; 1995.
Abstract
The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.
Url:
DOI: 10.1016/0197-0186(95)00137-9
Links to Exploration step
ISTEX:F3C6602BC4380A748340D459BF4F8F886875A3BELe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title><author><name sortKey="Gebicke Haerter, Peter J" sort="Gebicke Haerter, Peter J" uniqKey="Gebicke Haerter P" first="Peter J" last="Gebicke-Haerter">Peter J. Gebicke-Haerter</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Christoffel, Florian" sort="Christoffel, Florian" uniqKey="Christoffel F" first="Florian" last="Christoffel">Florian Christoffel</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Timmer, Jens" sort="Timmer, Jens" uniqKey="Timmer J" first="Jens" last="Timmer">Jens Timmer</name><affiliation><mods:affiliation>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Northoff, Hinnak" sort="Northoff, Hinnak" uniqKey="Northoff H" first="Hinnak" last="Northoff">Hinnak Northoff</name><affiliation><mods:affiliation>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Berger, Mathias" sort="Berger, Mathias" uniqKey="Berger M" first="Mathias" last="Berger">Mathias Berger</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Van Calker, Dietrich" sort="Van Calker, Dietrich" uniqKey="Van Calker D" first="Dietrich" last="Van Calker">Dietrich Van Calker</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:F3C6602BC4380A748340D459BF4F8F886875A3BE</idno><date when="1996" year="1996">1996</date><idno type="doi">10.1016/0197-0186(95)00137-9</idno><idno type="url">https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002F66</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title><author><name sortKey="Gebicke Haerter, Peter J" sort="Gebicke Haerter, Peter J" uniqKey="Gebicke Haerter P" first="Peter J" last="Gebicke-Haerter">Peter J. Gebicke-Haerter</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Christoffel, Florian" sort="Christoffel, Florian" uniqKey="Christoffel F" first="Florian" last="Christoffel">Florian Christoffel</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Timmer, Jens" sort="Timmer, Jens" uniqKey="Timmer J" first="Jens" last="Timmer">Jens Timmer</name><affiliation><mods:affiliation>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Northoff, Hinnak" sort="Northoff, Hinnak" uniqKey="Northoff H" first="Hinnak" last="Northoff">Hinnak Northoff</name><affiliation><mods:affiliation>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Berger, Mathias" sort="Berger, Mathias" uniqKey="Berger M" first="Mathias" last="Berger">Mathias Berger</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author><author><name sortKey="Van Calker, Dietrich" sort="Van Calker, Dietrich" uniqKey="Van Calker D" first="Dietrich" last="Van Calker">Dietrich Van Calker</name><affiliation><mods:affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Neurochemistry International</title><title level="j" type="abbrev">NCI</title><idno type="ISSN">0197-0186</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995">1995</date><biblScope unit="volume">29</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="37">37</biblScope><biblScope unit="page" to="42">42</biblScope></imprint><idno type="ISSN">0197-0186</idno></series><idno type="istex">F3C6602BC4380A748340D459BF4F8F886875A3BE</idno><idno type="DOI">10.1016/0197-0186(95)00137-9</idno><idno type="PII">0197-0186(95)00137-9</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0197-0186</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>PETER J GEBICKE-HAERTER</name><affiliations><json:string>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</json:string></affiliations></json:item><json:item><name>FLORIAN CHRISTOFFEL</name><affiliations><json:string>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</json:string></affiliations></json:item><json:item><name>JENS TIMMER</name><affiliations><json:string>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</json:string></affiliations></json:item><json:item><name>HINNAK NORTHOFF</name><affiliations><json:string>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>MATHIAS BERGER</name><affiliations><json:string>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</json:string></affiliations></json:item><json:item><name>DIETRICH VAN CALKER</name><affiliations><json:string>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</json:string></affiliations></json:item></author><language><json:string>eng</json:string></language><abstract>The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.</abstract><qualityIndicators><score>6.025</score><pdfVersion>1.1</pdfVersion><pdfPageSize>505 x 665 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1660</abstractCharCount><pdfWordCount>3325</pdfWordCount><pdfCharCount>23165</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>225</abstractWordCount></qualityIndicators><title>BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title><pii><json:string>0197-0186(95)00137-9</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>29</volume><pii><json:string>S0197-0186(00)X0030-7</json:string></pii><pages><last>42</last><first>37</first></pages><issn><json:string>0197-0186</json:string></issn><issue>1</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Neurochemistry International</title><publicationDate>1996</publicationDate></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>1995</publicationDate><copyrightDate>1996</copyrightDate><doi><json:string>10.1016/0197-0186(95)00137-9</json:string></doi><id>F3C6602BC4380A748340D459BF4F8F886875A3BE</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1996</date></publicationStmt><notesStmt><note>This is one of eight original papers on the subject “microglia”. Dr Peter Gebicke-Haerter (Dept. Psychiatry, University of Freiburg, Germany) acted as organiser and executive editor in the refereeing of these articles.</note><note type="content">Section title: COMMENTARY</note><note type="content">Fig. 1: [3H]Thymidine incorporation into microglial DNA upon incubation with adenosine A1- or A2-receptor agonists CPA or CGS-21680. Agonists were tested at 10−6 M-10−9 M. No effects different from controls (c1-c4) were observed at any concentration (10−8 M and 10−9 M not shown). Each condition was repeated at least three times, independently. For experimental details and calculations of relative values see Methods.</note><note type="content">Fig. 2: [3H]Thymidine incorporation into microglial DNA upon incubation with combinations of adenosine A1- and A2-receptor agonists. All combinations at concentrations of 10−6 M and 10−7 M increased microglial proliferation rates above controls (c1-c5). Lowering A2-receptor agonist concentrations relative to A1-receptor agonist apparently rather increased the effects. Each condition was repeated at least three times, independently. * P ⩽ 0.001 (for details of statistical evaluation see Methods).</note><note type="content">Fig. 3: [3H]Thymidine incorporation into microglial DNA upon incubation with the mixed agonist NECA. Incorporation was increased above controls (c1-c3) in a concentration-dependent manner. Each condition was repeated at least three thimes, independently. * P ⩽ 0.001 (for details of statistical evaluation see Methods).</note><note type="content">Fig. 4: Effect of the selective adenosine A1-receptor antagonist DPCPX on [3H]thymidine incorporation into microglial DNA in the presence of NECA. DPCPX (10−6 M) was added simultaneously with NECA (10−6 M) for 24 h. Concentrations of 10−7 M and 10−8 M DPCPX inhibited almost equally well (not shown; for data see text). DPCPX by itself showed a weak stimulatory effect which was not statistically significant. LPS (100 ng/ml) efficiently further reduced proliferation rates below untreated controls (c1-c4). Each condition was repeated at least three times, independently. NECA and LPS were significantly different from controls. * P ⩽ 0.001.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title><author><persName><forename type="first">PETER J</forename><surname>GEBICKE-HAERTER</surname></persName><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation></author><author><persName><forename type="first">FLORIAN</forename><surname>CHRISTOFFEL</surname></persName><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation></author><author><persName><forename type="first">JENS</forename><surname>TIMMER</surname></persName><affiliation>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</affiliation></author><author><persName><forename type="first">HINNAK</forename><surname>NORTHOFF</surname></persName><affiliation>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</affiliation></author><author><persName><forename type="first">MATHIAS</forename><surname>BERGER</surname></persName><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation></author><author><persName><forename type="first">DIETRICH</forename><surname>VAN CALKER</surname></persName><affiliation>Author to whom all correspondence should be addressed.</affiliation><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation></author></analytic><monogr><title level="j">Neurochemistry International</title><title level="j" type="abbrev">NCI</title><idno type="pISSN">0197-0186</idno><idno type="PII">S0197-0186(00)X0030-7</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995"></date><biblScope unit="volume">29</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="37">37</biblScope><biblScope unit="page" to="42">42</biblScope></imprint></monogr><idno type="istex">F3C6602BC4380A748340D459BF4F8F886875A3BE</idno><idno type="DOI">10.1016/0197-0186(95)00137-9</idno><idno type="PII">0197-0186(95)00137-9</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1996</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.</p></abstract></profileDesc><revisionDesc><change when="1995-10-21">Registration</change><change when="1995">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>NCI</jid><aid>361</aid><ce:pii>0197-0186(95)00137-9</ce:pii><ce:doi>10.1016/0197-0186(95)00137-9</ce:doi><ce:copyright year="1996" type="full-transfer">Elsevier Science Ltd</ce:copyright></item-info><head><ce:dochead><ce:textfn>COMMENTARY</ce:textfn></ce:dochead><ce:title>BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION<ce:cross-ref refid="FN1">*</ce:cross-ref><ce:footnote id="FN1"><ce:label>*</ce:label><ce:note-para>This is one of eight original papers on the subject “microglia”. Dr Peter Gebicke-Haerter (Dept. Psychiatry, University of Freiburg, Germany) acted as organiser and executive editor in the refereeing of these articles.</ce:note-para></ce:footnote></ce:title><ce:author-group><ce:author><ce:given-name>PETER J</ce:given-name><ce:surname>GEBICKE-HAERTER</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>FLORIAN</ce:given-name><ce:surname>CHRISTOFFEL</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>JENS</ce:given-name><ce:surname>TIMMER</ce:surname><ce:cross-ref refid="AFF2">b</ce:cross-ref></ce:author><ce:author><ce:given-name>HINNAK</ce:given-name><ce:surname>NORTHOFF</ce:surname><ce:cross-ref refid="AFF3">c</ce:cross-ref></ce:author><ce:author><ce:given-name>MATHIAS</ce:given-name><ce:surname>BERGER</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>DIETRICH</ce:given-name><ce:surname>VAN CALKER</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Author to whom all correspondence should be addressed.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="29" month="4" year="1995"></ce:date-received><ce:date-accepted day="21" month="10" year="1995"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [<ce:sup loc="pre">3</ce:sup>H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N<ce:sup>6</ce:sup>-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N<ce:sup>6</ce:sup>-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.</ce:simple-para></ce:abstract-sec></ce:abstract></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION</title></titleInfo><name type="personal"><namePart type="given">PETER J</namePart><namePart type="family">GEBICKE-HAERTER</namePart><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">FLORIAN</namePart><namePart type="family">CHRISTOFFEL</namePart><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">JENS</namePart><namePart type="family">TIMMER</namePart><affiliation>Institute of Physics, Hermann-Herder-Strasse 3, D-79104, Freiburg i.Br., Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">HINNAK</namePart><namePart type="family">NORTHOFF</namePart><affiliation>Department of Transfusion Medicine with Blood Bank, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">MATHIAS</namePart><namePart type="family">BERGER</namePart><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">DIETRICH</namePart><namePart type="family">VAN CALKER</namePart><affiliation>Department of Psychiatry, University of Freiburg Medical School, Hauptrasse 5, D-79104, Freiburg i.Br., Germany</affiliation><description>Author to whom all correspondence should be addressed.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1995</dateIssued><dateValid encoding="w3cdtf">1995-10-21</dateValid><copyrightDate encoding="w3cdtf">1996</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.</abstract><note type="footnote">This is one of eight original papers on the subject “microglia”. Dr Peter Gebicke-Haerter (Dept. Psychiatry, University of Freiburg, Germany) acted as organiser and executive editor in the refereeing of these articles.</note><note type="content">Section title: COMMENTARY</note><note type="content">Fig. 1: [3H]Thymidine incorporation into microglial DNA upon incubation with adenosine A1- or A2-receptor agonists CPA or CGS-21680. Agonists were tested at 10−6 M-10−9 M. No effects different from controls (c1-c4) were observed at any concentration (10−8 M and 10−9 M not shown). Each condition was repeated at least three times, independently. For experimental details and calculations of relative values see Methods.</note><note type="content">Fig. 2: [3H]Thymidine incorporation into microglial DNA upon incubation with combinations of adenosine A1- and A2-receptor agonists. All combinations at concentrations of 10−6 M and 10−7 M increased microglial proliferation rates above controls (c1-c5). Lowering A2-receptor agonist concentrations relative to A1-receptor agonist apparently rather increased the effects. Each condition was repeated at least three times, independently. * P ⩽ 0.001 (for details of statistical evaluation see Methods).</note><note type="content">Fig. 3: [3H]Thymidine incorporation into microglial DNA upon incubation with the mixed agonist NECA. Incorporation was increased above controls (c1-c3) in a concentration-dependent manner. Each condition was repeated at least three thimes, independently. * P ⩽ 0.001 (for details of statistical evaluation see Methods).</note><note type="content">Fig. 4: Effect of the selective adenosine A1-receptor antagonist DPCPX on [3H]thymidine incorporation into microglial DNA in the presence of NECA. DPCPX (10−6 M) was added simultaneously with NECA (10−6 M) for 24 h. Concentrations of 10−7 M and 10−8 M DPCPX inhibited almost equally well (not shown; for data see text). DPCPX by itself showed a weak stimulatory effect which was not statistically significant. LPS (100 ng/ml) efficiently further reduced proliferation rates below untreated controls (c1-c4). Each condition was repeated at least three times, independently. NECA and LPS were significantly different from controls. * P ⩽ 0.001.</note><relatedItem type="host"><titleInfo><title>Neurochemistry International</title></titleInfo><titleInfo type="abbreviated"><title>NCI</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199607</dateIssued></originInfo><identifier type="ISSN">0197-0186</identifier><identifier type="PII">S0197-0186(00)X0030-7</identifier><part><date>199607</date><detail type="volume"><number>29</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>96</end></extent><extent unit="pages"><start>37</start><end>42</end></extent></part></relatedItem><identifier type="istex">F3C6602BC4380A748340D459BF4F8F886875A3BE</identifier><identifier type="DOI">10.1016/0197-0186(95)00137-9</identifier><identifier type="PII">0197-0186(95)00137-9</identifier><accessCondition type="use and reproduction" contentType="">© 1996Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science Ltd, ©1996</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/F3C6602BC4380A748340D459BF4F8F886875A3BE/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002F66 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 002F66 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:F3C6602BC4380A748340D459BF4F8F886875A3BE
|texte= BOTH ADENOSINE A1- AND A2-RECEPTORS ARE REQUIRED TO STIMULATE MICROGLIAL PROLIFERATION
}}
| This area was generated with Dilib version V0.6.23. |  |