Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus
While group II metabotropic glutamate receptors (mGluRs) are known to be expressed in the rat globus pallidus (GP), their functions remain poorly understood. We used standard patch clamping technique in GP slices to determine the effect of group II mGluR activation on excitatory transmission in this...
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| Veröffentlicht in: | Neuropharmacology 2005, Vol.49, p.57-69 |
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| creator | Poisik, Olga Raju, Dinesh V. Verreault, Marc Rodriguez, Alice Abeniyi, Oluseyi A. Conn, P. Jeffrey Smith, Yoland |
| description | While group II metabotropic glutamate receptors (mGluRs) are known to be expressed in the rat globus pallidus (GP), their functions remain poorly understood. We used standard patch clamping technique in GP slices to determine the effect of group II mGluR activation on excitatory transmission in this region. Activation of group II mGluRs with the group-selective agonist DCG-IV or APDC reduced the amplitude of the evoked excitatory postsynaptic currents (EPSCs) and significantly increased the paired pulse ratio suggesting a presynaptic site of action. This was further supported by double-labeling electron microscopy data showing that group II mGluRs (mGluR2 and 3) immunoreactivity is localized in glutamatergic pre-terminal axons and terminals in the GP. Furthermore, we found that LY 487379, an mGluR2-specific allosteric modulator, significantly potentiated the inhibitory effect of DCG-IV on the excitatory transmission in the GP. Co-incubation with 30
μM LY 487379 increased the potency of DCG-IV about 10-fold in the GP.
We were thus able to pharmacologically isolate the mGluR2-mediated function in the rat GP using an mGluR2-specific allosteric modulator. Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease. |
| doi_str_mv | 10.1016/j.neuropharm.2005.03.006 |
| format | Article |
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μM LY 487379 increased the potency of DCG-IV about 10-fold in the GP.
We were thus able to pharmacologically isolate the mGluR2-mediated function in the rat GP using an mGluR2-specific allosteric modulator. Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/j.neuropharm.2005.03.006</identifier><identifier>PMID: 15993439</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology ; Allosteric modulators ; Amino Acids - pharmacology ; Aminobutyrates - pharmacology ; Anesthetics, Local - pharmacology ; Animals ; Animals, Newborn ; Cyclopropanes - pharmacology ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Drug Interactions ; Electric Stimulation - methods ; Excitatory Amino Acid Agonists - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - physiology ; Excitatory Postsynaptic Potentials - radiation effects ; Excitatory transmission ; Globus pallidus ; Globus Pallidus - cytology ; Glycine - analogs & derivatives ; Glycine - pharmacology ; Group II ; In Vitro Techniques ; Lidocaine - analogs & derivatives ; Lidocaine - pharmacology ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Membrane Potentials - radiation effects ; Metabotropic glutamate receptors ; Methoxyhydroxyphenylglycol - analogs & derivatives ; Methoxyhydroxyphenylglycol - pharmacology ; Neurons - drug effects ; Neurons - physiology ; Neurons - radiation effects ; Parkinson's disease ; Patch-Clamp Techniques - methods ; Proline - analogs & derivatives ; Proline - pharmacology ; Pyridines - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA - physiology ; Sulfonamides - pharmacology ; Synaptic Transmission - drug effects ; Synaptic Transmission - physiology ; Synaptic Transmission - radiation effects ; Xanthenes - pharmacology</subject><ispartof>Neuropharmacology, 2005, Vol.49, p.57-69</ispartof><rights>2005 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c403t-7b72d248ca4d79cb41a37f1b1c084b9d3e405e2027935ecd2374954bebfd024d3</citedby><cites>FETCH-LOGICAL-c403t-7b72d248ca4d79cb41a37f1b1c084b9d3e405e2027935ecd2374954bebfd024d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuropharm.2005.03.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,4009,27902,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15993439$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poisik, Olga</creatorcontrib><creatorcontrib>Raju, Dinesh V.</creatorcontrib><creatorcontrib>Verreault, Marc</creatorcontrib><creatorcontrib>Rodriguez, Alice</creatorcontrib><creatorcontrib>Abeniyi, Oluseyi A.</creatorcontrib><creatorcontrib>Conn, P. Jeffrey</creatorcontrib><creatorcontrib>Smith, Yoland</creatorcontrib><title>Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>While group II metabotropic glutamate receptors (mGluRs) are known to be expressed in the rat globus pallidus (GP), their functions remain poorly understood. We used standard patch clamping technique in GP slices to determine the effect of group II mGluR activation on excitatory transmission in this region. Activation of group II mGluRs with the group-selective agonist DCG-IV or APDC reduced the amplitude of the evoked excitatory postsynaptic currents (EPSCs) and significantly increased the paired pulse ratio suggesting a presynaptic site of action. This was further supported by double-labeling electron microscopy data showing that group II mGluRs (mGluR2 and 3) immunoreactivity is localized in glutamatergic pre-terminal axons and terminals in the GP. Furthermore, we found that LY 487379, an mGluR2-specific allosteric modulator, significantly potentiated the inhibitory effect of DCG-IV on the excitatory transmission in the GP. Co-incubation with 30
μM LY 487379 increased the potency of DCG-IV about 10-fold in the GP.
We were thus able to pharmacologically isolate the mGluR2-mediated function in the rat GP using an mGluR2-specific allosteric modulator. Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease.</description><subject>6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology</subject><subject>Allosteric modulators</subject><subject>Amino Acids - pharmacology</subject><subject>Aminobutyrates - pharmacology</subject><subject>Anesthetics, Local - pharmacology</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Cyclopropanes - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Drug Interactions</subject><subject>Electric Stimulation - methods</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Excitatory Postsynaptic Potentials - radiation effects</subject><subject>Excitatory transmission</subject><subject>Globus pallidus</subject><subject>Globus Pallidus - cytology</subject><subject>Glycine - analogs & derivatives</subject><subject>Glycine - pharmacology</subject><subject>Group II</subject><subject>In Vitro Techniques</subject><subject>Lidocaine - analogs & derivatives</subject><subject>Lidocaine - pharmacology</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Membrane Potentials - radiation effects</subject><subject>Metabotropic glutamate receptors</subject><subject>Methoxyhydroxyphenylglycol - analogs & derivatives</subject><subject>Methoxyhydroxyphenylglycol - pharmacology</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Neurons - radiation effects</subject><subject>Parkinson's disease</subject><subject>Patch-Clamp Techniques - methods</subject><subject>Proline - analogs & derivatives</subject><subject>Proline - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, AMPA - physiology</subject><subject>Sulfonamides - pharmacology</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synaptic Transmission - physiology</subject><subject>Synaptic Transmission - radiation effects</subject><subject>Xanthenes - pharmacology</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1P3DAQxa2Kqiy0_0LlE7eE8UfWybFFQCtR9dKeLX_MgldJnNoOYv_7Gu1KHDmNNHrvzbwfIZRBy4Btr_ftjGuKy5NJU8sBuhZEC7D9QDasV6JRsJVnZAPA-0YM0J-Ti5z3ACB71n8i56wbBiHFsCGPv7AYG0sNC44-jmsxkylIEzpcSkyU0yn6day7TPHFhWLq9kDzYTZLqZaSzJynkHOIMw0zLU_VbEqNinbNdDHjGPyaP5OPOzNm_HKal-Tv3e2fmx_Nw-_7nzffHhonQZRGWcU9l70z0qvBWcmMUDtmmYNe2sELlNAhB64G0aHzXCg5dNKi3Xng0otLcnXMXVL8t2Iuuv7mcBzNjHHNminZ1fayCvuj0KWYc8KdXlKYTDpoBvoVst7rN8j6FbIGoSvkav16urHaCf2b8US1Cr4fBVibPgdMOruAs0MfKteifQzvX_kPyOKV8Q</recordid><startdate>2005</startdate><enddate>2005</enddate><creator>Poisik, Olga</creator><creator>Raju, Dinesh V.</creator><creator>Verreault, Marc</creator><creator>Rodriguez, Alice</creator><creator>Abeniyi, Oluseyi A.</creator><creator>Conn, P. Jeffrey</creator><creator>Smith, Yoland</creator><general>Elsevier Ltd</general><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>7TK</scope></search><sort><creationdate>2005</creationdate><title>Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus</title><author>Poisik, Olga ; Raju, Dinesh V. ; Verreault, Marc ; Rodriguez, Alice ; Abeniyi, Oluseyi A. ; Conn, P. Jeffrey ; Smith, Yoland</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c403t-7b72d248ca4d79cb41a37f1b1c084b9d3e405e2027935ecd2374954bebfd024d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology</topic><topic>Allosteric modulators</topic><topic>Amino Acids - pharmacology</topic><topic>Aminobutyrates - pharmacology</topic><topic>Anesthetics, Local - pharmacology</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Cyclopropanes - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Drug Interactions</topic><topic>Electric Stimulation - methods</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Excitatory Postsynaptic Potentials - radiation effects</topic><topic>Excitatory transmission</topic><topic>Globus pallidus</topic><topic>Globus Pallidus - cytology</topic><topic>Glycine - analogs & derivatives</topic><topic>Glycine - pharmacology</topic><topic>Group II</topic><topic>In Vitro Techniques</topic><topic>Lidocaine - analogs & derivatives</topic><topic>Lidocaine - pharmacology</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Membrane Potentials - radiation effects</topic><topic>Metabotropic glutamate receptors</topic><topic>Methoxyhydroxyphenylglycol - analogs & derivatives</topic><topic>Methoxyhydroxyphenylglycol - pharmacology</topic><topic>Neurons - drug effects</topic><topic>Neurons - physiology</topic><topic>Neurons - radiation effects</topic><topic>Parkinson's disease</topic><topic>Patch-Clamp Techniques - methods</topic><topic>Proline - analogs & derivatives</topic><topic>Proline - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, AMPA - physiology</topic><topic>Sulfonamides - pharmacology</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synaptic Transmission - physiology</topic><topic>Synaptic Transmission - radiation effects</topic><topic>Xanthenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Poisik, Olga</creatorcontrib><creatorcontrib>Raju, Dinesh V.</creatorcontrib><creatorcontrib>Verreault, Marc</creatorcontrib><creatorcontrib>Rodriguez, Alice</creatorcontrib><creatorcontrib>Abeniyi, Oluseyi A.</creatorcontrib><creatorcontrib>Conn, P. Jeffrey</creatorcontrib><creatorcontrib>Smith, Yoland</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poisik, Olga</au><au>Raju, Dinesh V.</au><au>Verreault, Marc</au><au>Rodriguez, Alice</au><au>Abeniyi, Oluseyi A.</au><au>Conn, P. Jeffrey</au><au>Smith, Yoland</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>2005</date><risdate>2005</risdate><volume>49</volume><spage>57</spage><epage>69</epage><pages>57-69</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><abstract>While group II metabotropic glutamate receptors (mGluRs) are known to be expressed in the rat globus pallidus (GP), their functions remain poorly understood. We used standard patch clamping technique in GP slices to determine the effect of group II mGluR activation on excitatory transmission in this region. Activation of group II mGluRs with the group-selective agonist DCG-IV or APDC reduced the amplitude of the evoked excitatory postsynaptic currents (EPSCs) and significantly increased the paired pulse ratio suggesting a presynaptic site of action. This was further supported by double-labeling electron microscopy data showing that group II mGluRs (mGluR2 and 3) immunoreactivity is localized in glutamatergic pre-terminal axons and terminals in the GP. Furthermore, we found that LY 487379, an mGluR2-specific allosteric modulator, significantly potentiated the inhibitory effect of DCG-IV on the excitatory transmission in the GP. Co-incubation with 30
μM LY 487379 increased the potency of DCG-IV about 10-fold in the GP.
We were thus able to pharmacologically isolate the mGluR2-mediated function in the rat GP using an mGluR2-specific allosteric modulator. Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>15993439</pmid><doi>10.1016/j.neuropharm.2005.03.006</doi><tpages>13</tpages></addata></record> |
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| subjects | 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology Allosteric modulators Amino Acids - pharmacology Aminobutyrates - pharmacology Anesthetics, Local - pharmacology Animals Animals, Newborn Cyclopropanes - pharmacology Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Drug Interactions Electric Stimulation - methods Excitatory Amino Acid Agonists - pharmacology Excitatory Amino Acid Antagonists - pharmacology Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - physiology Excitatory Postsynaptic Potentials - radiation effects Excitatory transmission Globus pallidus Globus Pallidus - cytology Glycine - analogs & derivatives Glycine - pharmacology Group II In Vitro Techniques Lidocaine - analogs & derivatives Lidocaine - pharmacology Membrane Potentials - drug effects Membrane Potentials - physiology Membrane Potentials - radiation effects Metabotropic glutamate receptors Methoxyhydroxyphenylglycol - analogs & derivatives Methoxyhydroxyphenylglycol - pharmacology Neurons - drug effects Neurons - physiology Neurons - radiation effects Parkinson's disease Patch-Clamp Techniques - methods Proline - analogs & derivatives Proline - pharmacology Pyridines - pharmacology Rats Rats, Sprague-Dawley Receptors, AMPA - physiology Sulfonamides - pharmacology Synaptic Transmission - drug effects Synaptic Transmission - physiology Synaptic Transmission - radiation effects Xanthenes - pharmacology |
| title | Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus |
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