Presynaptic adenosine A2A receptors dampen cannabinoid CB1 receptor-mediated inhibition of corticostriatal glutamatergic transmission
Identifieur interne : 000430 ( Pmc/Curation ); précédent : 000429; suivant : 000431Presynaptic adenosine A2A receptors dampen cannabinoid CB1 receptor-mediated inhibition of corticostriatal glutamatergic transmission
Auteurs : S G Ferreira [Portugal] ; F Q Gonçalves [Portugal] ; J M Marques [Portugal] ; Â R. Tomé [Portugal] ; R J Rodrigues [Portugal] ; I. Nunes-Correia [Portugal] ; C. Ledent [Suède] ; T. Harkany [Suède, Autriche] ; L. Venance [France] ; R A Cunha [Portugal] ; A. Köfalvi [Portugal]Source :
- British Journal of Pharmacology [ 0007-1188 ] ; 2015.
Abstract
Both cannabinoid CB1 and adenosine A2A receptors (CB1 receptors and A2A receptors) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A postsynaptic CB1−A2A receptor interaction has already been elucidated, but the presynaptic A2A receptor-mediated control of presynaptic neuromodulation by CB1 receptors remains to be defined. Because the corticostriatal terminals provide the major input to the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions.
Pharmacological manipulation of CB1 and A2A receptors was carried out in brain nerve terminals isolated from rats and mice, using flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement. Whole-cell patch-clamp recordings were made in horizontal corticostriatal slices.
Flow synaptometry showed that A2A receptors were extensively co-localized with CB1 receptor-immunopositive corticostriatal terminals and A2A receptors co-immunoprecipitated CB1 receptors in these purified terminals. A2A receptor activation decreased CB1 receptor radioligand binding and decreased the CB1 receptor-mediated inhibition of high-K+-evoked glutamate release in corticostriatal terminals. Accordingly, A2A receptor activation prevented CB1 receptor-mediated paired-pulse facilitation and attenuated the CB1 receptor-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices.
Activation of presynaptic A2A receptors dampened CB1 receptor-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to modulate the potent CB1 receptor-mediated presynaptic inhibition, allowing frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses.
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DOI: 10.1111/bph.12970
PubMed: 25296982
PubMed Central: 4314196
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Harkany</name><affiliation wicri:level="1"><nlm:aff id="au9"><institution>Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet</institution><addr-line>S-17177, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>S-17177, Stockholm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au10"><institution>Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna</institution><addr-line>Spitalgasse 4, A-1090, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Spitalgasse 4, A-1090, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Venance, L" sort="Venance, L" uniqKey="Venance L" first="L" last="Venance">L. 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Köfalvi</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Laboratory of Neuromodulation and Metabolism, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au7"><institution>Institute for Interdisciplinary Research, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25296982</idno><idno type="pmc">4314196</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314196</idno><idno type="RBID">PMC:4314196</idno><idno type="doi">10.1111/bph.12970</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000433</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000433</idno><idno type="wicri:Area/Pmc/Curation">000430</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000430</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Presynaptic adenosine A<sub>2A</sub> receptors dampen cannabinoid CB<sub>1</sub> receptor-mediated inhibition of corticostriatal glutamatergic transmission</title><author><name sortKey="Ferreira, S G" sort="Ferreira, S G" uniqKey="Ferreira S" first="S G" last="Ferreira">S G Ferreira</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Laboratory of Neuromodulation and Metabolism, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Doctoral Programme in Experimental Biology and Biomedicine, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, C356:514 oimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, C356:514 oimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au4"><institution>Faculty of Medicine, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Goncalves, F Q" sort="Goncalves, F Q" uniqKey="Goncalves F" first="F Q" last="Gonçalves">F Q Gonçalves</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Marques, J M" sort="Marques, J M" uniqKey="Marques J" first="J M" last="Marques">J M Marques</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Tome, A R" sort="Tome, A R" uniqKey="Tome A" first="Â R" last="Tomé">Â R. Tomé</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Rodrigues, R J" sort="Rodrigues, R J" uniqKey="Rodrigues R" first="R J" last="Rodrigues">R J Rodrigues</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Nunes Correia, I" sort="Nunes Correia, I" uniqKey="Nunes Correia I" first="I" last="Nunes-Correia">I. Nunes-Correia</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Flow Cytometry Unit, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Ledent, C" sort="Ledent, C" uniqKey="Ledent C" first="C" last="Ledent">C. Ledent</name><affiliation wicri:level="1"><nlm:aff id="au8"><institution>IRIBHM, Université Libre de Bruxelles</institution><addr-line>Brussels, B-1070, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Brussels, B-1070</wicri:regionArea></affiliation></author><author><name sortKey="Harkany, T" sort="Harkany, T" uniqKey="Harkany T" first="T" last="Harkany">T. Harkany</name><affiliation wicri:level="1"><nlm:aff id="au9"><institution>Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet</institution><addr-line>S-17177, Stockholm, Sweden</addr-line></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>S-17177, Stockholm</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au10"><institution>Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna</institution><addr-line>Spitalgasse 4, A-1090, Vienna, Austria</addr-line></nlm:aff><country xml:lang="fr">Autriche</country><wicri:regionArea>Spitalgasse 4, A-1090, Vienna</wicri:regionArea></affiliation></author><author><name sortKey="Venance, L" sort="Venance, L" uniqKey="Venance L" first="L" last="Venance">L. Venance</name><affiliation wicri:level="1"><nlm:aff id="au11"><institution>Team Dynamic and Pathophysiology of Neuronal Networks, Center for Interdisciplinary Research in Biology, College de France, CNRS UMR7241/INSERM U1050</institution><addr-line>Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris</wicri:regionArea></affiliation></author><author><name sortKey="Cunha, R A" sort="Cunha, R A" uniqKey="Cunha R" first="R A" last="Cunha">R A Cunha</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au4"><institution>Faculty of Medicine, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author><author><name sortKey="Kofalvi, A" sort="Kofalvi, A" uniqKey="Kofalvi A" first="A" last="Köfalvi">A. Köfalvi</name><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Laboratory of Neuromodulation and Metabolism, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au7"><institution>Institute for Interdisciplinary Research, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>3004-504, Coimbra</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Pharmacology</title><idno type="ISSN">0007-1188</idno><idno type="eISSN">1476-5381</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background and Purpose</title><p>Both cannabinoid CB<sub>1</sub> and adenosine A<sub>2A</sub> receptors (CB<sub>1</sub> receptors and A<sub>2A</sub> receptors) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A postsynaptic CB<sub>1</sub>−A<sub>2A</sub> receptor interaction has already been elucidated, but the presynaptic A<sub>2A</sub> receptor-mediated control of presynaptic neuromodulation by CB<sub>1</sub> receptors remains to be defined. Because the corticostriatal terminals provide the major input to the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions.</p></sec><sec><title>Experimental Approach</title><p>Pharmacological manipulation of CB<sub>1</sub> and A<sub>2A</sub> receptors was carried out in brain nerve terminals isolated from rats and mice, using flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement. Whole-cell patch-clamp recordings were made in horizontal corticostriatal slices.</p></sec><sec><title>Key Results</title><p>Flow synaptometry showed that A<sub>2A</sub> receptors were extensively co-localized with CB<sub>1</sub> receptor-immunopositive corticostriatal terminals and A<sub>2A</sub> receptors co-immunoprecipitated CB<sub>1</sub> receptors in these purified terminals. A<sub>2A</sub> receptor activation decreased CB<sub>1</sub> receptor radioligand binding and decreased the CB<sub>1</sub> receptor-mediated inhibition of high-K<sup>+</sup>-evoked glutamate release in corticostriatal terminals. Accordingly, A<sub>2A</sub> receptor activation prevented CB<sub>1</sub> receptor-mediated paired-pulse facilitation and attenuated the CB<sub>1</sub> receptor-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices.</p></sec><sec><title>Conclusions and Implications</title><p>Activation of presynaptic A<sub>2A</sub> receptors dampened CB<sub>1</sub> receptor-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to modulate the potent CB<sub>1</sub> receptor-mediated presynaptic inhibition, allowing frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Br. J. Pharmacol</journal-id><journal-id journal-id-type="publisher-id">bph</journal-id><journal-title-group><journal-title>British Journal of Pharmacology</journal-title></journal-title-group><issn pub-type="ppub">0007-1188</issn><issn pub-type="epub">1476-5381</issn><publisher><publisher-name>BlackWell Publishing Ltd</publisher-name><publisher-loc>Oxford, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25296982</article-id><article-id pub-id-type="pmc">4314196</article-id><article-id pub-id-type="doi">10.1111/bph.12970</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Papers</subject></subj-group></article-categories><title-group><article-title>Presynaptic adenosine A<sub>2A</sub> receptors dampen cannabinoid CB<sub>1</sub> receptor-mediated inhibition of corticostriatal glutamatergic transmission</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ferreira</surname><given-names>S G</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au3">3</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Gonçalves</surname><given-names>F Q</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Marques</surname><given-names>J M</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tomé</surname><given-names>Â R</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rodrigues</surname><given-names>R J</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Nunes-Correia</surname><given-names>I</given-names></name><xref ref-type="aff" rid="au6">6</xref></contrib><contrib contrib-type="author"><name><surname>Ledent</surname><given-names>C</given-names></name><xref ref-type="aff" rid="au8">8</xref></contrib><contrib contrib-type="author"><name><surname>Harkany</surname><given-names>T</given-names></name><xref ref-type="aff" rid="au9">9</xref><xref ref-type="aff" rid="au10">10</xref></contrib><contrib contrib-type="author"><name><surname>Venance</surname><given-names>L</given-names></name><xref ref-type="aff" rid="au11">11</xref></contrib><contrib contrib-type="author"><name><surname>Cunha</surname><given-names>R A</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Köfalvi</surname><given-names>A</given-names></name><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au7">7</xref><xref ref-type="corresp" rid="cor1"></xref></contrib><aff id="au1"><label>1</label><institution>Neuromodulation Group, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au2"><label>2</label><institution>Laboratory of Neuromodulation and Metabolism, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au3"><label>3</label><institution>Doctoral Programme in Experimental Biology and Biomedicine, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, C356:514 oimbra, Portugal</addr-line></aff><aff id="au4"><label>4</label><institution>Faculty of Medicine, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au5"><label>5</label><institution>Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au6"><label>6</label><institution>Flow Cytometry Unit, CNC-Center for Neuroscience and Cell Biology, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au7"><label>7</label><institution>Institute for Interdisciplinary Research, University of Coimbra</institution><addr-line>3004-504, Coimbra, Portugal</addr-line></aff><aff id="au8"><label>8</label><institution>IRIBHM, Université Libre de Bruxelles</institution><addr-line>Brussels, B-1070, Sweden</addr-line></aff><aff id="au9"><label>9</label><institution>Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet</institution><addr-line>S-17177, Stockholm, Sweden</addr-line></aff><aff id="au10"><label>10</label><institution>Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna</institution><addr-line>Spitalgasse 4, A-1090, Vienna, Austria</addr-line></aff><aff id="au11"><label>11</label><institution>Team Dynamic and Pathophysiology of Neuronal Networks, Center for Interdisciplinary Research in Biology, College de France, CNRS UMR7241/INSERM U1050</institution><addr-line>Paris, France</addr-line></aff></contrib-group><author-notes><corresp id="cor1"><bold>Correspondence</bold>, Dr A Köfalvi, Laboratory of Neuromodulation and Metabolism, Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal. E-mail: <email>akofalvi@uc.pt</email></corresp></author-notes><pub-date pub-type="ppub"><month>2</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>12</day><month>1</month><year>2015</year></pub-date><volume>172</volume><issue>4</issue><fpage>1074</fpage><lpage>1086</lpage><history><date date-type="received"><day>12</day><month>7</month><year>2014</year></date><date date-type="rev-recd"><day>30</day><month>9</month><year>2014</year></date><date date-type="accepted"><day>03</day><month>10</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 The British Pharmacological Society</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><sec><title>Background and Purpose</title><p>Both cannabinoid CB<sub>1</sub> and adenosine A<sub>2A</sub> receptors (CB<sub>1</sub> receptors and A<sub>2A</sub> receptors) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A postsynaptic CB<sub>1</sub>−A<sub>2A</sub> receptor interaction has already been elucidated, but the presynaptic A<sub>2A</sub> receptor-mediated control of presynaptic neuromodulation by CB<sub>1</sub> receptors remains to be defined. Because the corticostriatal terminals provide the major input to the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions.</p></sec><sec><title>Experimental Approach</title><p>Pharmacological manipulation of CB<sub>1</sub> and A<sub>2A</sub> receptors was carried out in brain nerve terminals isolated from rats and mice, using flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement. Whole-cell patch-clamp recordings were made in horizontal corticostriatal slices.</p></sec><sec><title>Key Results</title><p>Flow synaptometry showed that A<sub>2A</sub> receptors were extensively co-localized with CB<sub>1</sub> receptor-immunopositive corticostriatal terminals and A<sub>2A</sub> receptors co-immunoprecipitated CB<sub>1</sub> receptors in these purified terminals. A<sub>2A</sub> receptor activation decreased CB<sub>1</sub> receptor radioligand binding and decreased the CB<sub>1</sub> receptor-mediated inhibition of high-K<sup>+</sup>-evoked glutamate release in corticostriatal terminals. Accordingly, A<sub>2A</sub> receptor activation prevented CB<sub>1</sub> receptor-mediated paired-pulse facilitation and attenuated the CB<sub>1</sub> receptor-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices.</p></sec><sec><title>Conclusions and Implications</title><p>Activation of presynaptic A<sub>2A</sub> receptors dampened CB<sub>1</sub> receptor-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to modulate the potent CB<sub>1</sub> receptor-mediated presynaptic inhibition, allowing frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses.</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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