Dopamine Receptor Subtypes Colocalize in Rat Striatonigral Neurons
Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-11, Vol.89 (21), p.10178-10182 |
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| creator | Surmeier, D. J. Eberwine, J. Wilson, C. J. Cao, Y. Stefani, A. Kitai, S. T. |
| description | Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+current. The D2agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in wholecell recordings, whereas quinpirole consistently (6/10) enhanced currents-suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3receptors. |
| doi_str_mv | 10.1073/pnas.89.21.10178 |
| format | Article |
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J. ; Eberwine, J. ; Wilson, C. J. ; Cao, Y. ; Stefani, A. ; Kitai, S. T.</creator><creatorcontrib>Surmeier, D. J. ; Eberwine, J. ; Wilson, C. J. ; Cao, Y. ; Stefani, A. ; Kitai, S. T.</creatorcontrib><description>Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+current. The D2agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in wholecell recordings, whereas quinpirole consistently (6/10) enhanced currents-suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3receptors.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.21.10178</identifier><identifier>PMID: 1332033</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology ; Agonists ; Animals ; Antisense Elements (Genetics) ; Base Sequence ; Biological and medical sciences ; Blotting, Southern ; Bromocriptine - pharmacology ; Central nervous system ; characterization ; Complementary DNA ; Deoxyribonucleic acid ; DNA ; DNA - genetics ; DNA - isolation & purification ; dopamine ; Dopamine receptors ; Electric potential ; Electrophysiology ; Ergolines - pharmacology ; Evoked Potentials - drug effects ; Fundamental and applied biological sciences. Psychology ; Gels ; Medical research ; Messenger RNA ; Microscopy, Fluorescence ; Molecular Sequence Data ; neostriatum ; Neostriatum - cytology ; Neostriatum - physiology ; Neurology ; Neurons ; Neurons - cytology ; Neurons - physiology ; Neuroscience ; Oligodeoxyribonucleotides ; Polymerase chain reaction ; Quinpirole ; Rats ; Receptors ; Receptors, Dopamine - analysis ; Receptors, Dopamine - genetics ; Receptors, Dopamine - physiology ; Receptors, Dopamine D1 - analysis ; Receptors, Dopamine D1 - genetics ; Receptors, Dopamine D1 - physiology ; Receptors, Dopamine D2 - analysis ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - physiology ; Receptors, Dopamine D3 ; Ribonucleic acid ; RNA ; RNA Probes ; RNA, Messenger - genetics ; RNA, Messenger - isolation & purification ; Sodium Channels - drug effects ; Sodium Channels - physiology ; substantia nigra ; Substantia Nigra - cytology ; Substantia Nigra - physiology ; Vertebrates: nervous system and sense organs</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-11, Vol.89 (21), p.10178-10182</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1993 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Nov 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c620t-cefb34310e76443bb7caacc52516012b872819c8f09c323739d56f60ee6699923</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2360572$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2360572$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4499698$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1332033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Surmeier, D. J.</creatorcontrib><creatorcontrib>Eberwine, J.</creatorcontrib><creatorcontrib>Wilson, C. J.</creatorcontrib><creatorcontrib>Cao, Y.</creatorcontrib><creatorcontrib>Stefani, A.</creatorcontrib><creatorcontrib>Kitai, S. T.</creatorcontrib><title>Dopamine Receptor Subtypes Colocalize in Rat Striatonigral Neurons</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+current. The D2agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in wholecell recordings, whereas quinpirole consistently (6/10) enhanced currents-suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3receptors.</description><subject>2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology</subject><subject>Agonists</subject><subject>Animals</subject><subject>Antisense Elements (Genetics)</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Southern</subject><subject>Bromocriptine - pharmacology</subject><subject>Central nervous system</subject><subject>characterization</subject><subject>Complementary DNA</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>dopamine</subject><subject>Dopamine receptors</subject><subject>Electric potential</subject><subject>Electrophysiology</subject><subject>Ergolines - pharmacology</subject><subject>Evoked Potentials - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gels</subject><subject>Medical research</subject><subject>Messenger RNA</subject><subject>Microscopy, Fluorescence</subject><subject>Molecular Sequence Data</subject><subject>neostriatum</subject><subject>Neostriatum - cytology</subject><subject>Neostriatum - physiology</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - physiology</subject><subject>Neuroscience</subject><subject>Oligodeoxyribonucleotides</subject><subject>Polymerase chain reaction</subject><subject>Quinpirole</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Dopamine - analysis</subject><subject>Receptors, Dopamine - genetics</subject><subject>Receptors, Dopamine - physiology</subject><subject>Receptors, Dopamine D1 - analysis</subject><subject>Receptors, Dopamine D1 - genetics</subject><subject>Receptors, Dopamine D1 - physiology</subject><subject>Receptors, Dopamine D2 - analysis</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - physiology</subject><subject>Receptors, Dopamine D3</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Probes</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - isolation & purification</subject><subject>Sodium Channels - drug effects</subject><subject>Sodium Channels - physiology</subject><subject>substantia nigra</subject><subject>Substantia Nigra - cytology</subject><subject>Substantia Nigra - physiology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkkuLFDEUhYMoYzu6d6FYiIibam8elQe40fYJg8KMrkMqkxrTVCdlkhLHX2_ablvHha5CON-5ufeeIHQXwxKDoE-nYPJSqiXB9Y6FvIYWGBRuOVNwHS0AiGglI-wmupXzGgBUJ-EIHWFKCVC6QC9exslsfHDNqbNuKjE1Z3NfLieXm1UcozWj_-4aH5pTU5qzkrwpMfiLZMbmvZtTDPk2ujGYMbs7-_MYfXr96uPqbXvy4c271fOT1nICpbVu6CmjGJzgjNG-F9YYazvSYQ6Y9FIQiZWVAyhLCRVUnXd84OAc50opQo_Rs13dae437ty6UGoXekp-Y9Kljsbrq0rwn_VF_Ko7oICr_fHenuKX2eWiNz5bN44muDhnLepKFHT_BzHvMOOiq-DDv8B1nFOoO9CkTiSBE1kh2EE2xZyTGw4NY9DbDPU2Qy2VJlj_zLBa7v856G_DLrSqP9rrJtd8hmSC9fmAMaYUV9syD_bY9oFf6tWHnvyb0MM8jsV9KxW9t0PXuf6RA0soh04Q-gNt8MXG</recordid><startdate>19921101</startdate><enddate>19921101</enddate><creator>Surmeier, D. 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Psychology</topic><topic>Gels</topic><topic>Medical research</topic><topic>Messenger RNA</topic><topic>Microscopy, Fluorescence</topic><topic>Molecular Sequence Data</topic><topic>neostriatum</topic><topic>Neostriatum - cytology</topic><topic>Neostriatum - physiology</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - physiology</topic><topic>Neuroscience</topic><topic>Oligodeoxyribonucleotides</topic><topic>Polymerase chain reaction</topic><topic>Quinpirole</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Dopamine - analysis</topic><topic>Receptors, Dopamine - genetics</topic><topic>Receptors, Dopamine - physiology</topic><topic>Receptors, Dopamine D1 - analysis</topic><topic>Receptors, Dopamine D1 - genetics</topic><topic>Receptors, Dopamine D1 - physiology</topic><topic>Receptors, Dopamine D2 - analysis</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - physiology</topic><topic>Receptors, Dopamine D3</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Probes</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - isolation & purification</topic><topic>Sodium Channels - drug effects</topic><topic>Sodium Channels - physiology</topic><topic>substantia nigra</topic><topic>Substantia Nigra - cytology</topic><topic>Substantia Nigra - physiology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Surmeier, D. 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J.</au><au>Eberwine, J.</au><au>Wilson, C. J.</au><au>Cao, Y.</au><au>Stefani, A.</au><au>Kitai, S. T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dopamine Receptor Subtypes Colocalize in Rat Striatonigral Neurons</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-11-01</date><risdate>1992</risdate><volume>89</volume><issue>21</issue><spage>10178</spage><epage>10182</epage><pages>10178-10182</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+current. The D2agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in wholecell recordings, whereas quinpirole consistently (6/10) enhanced currents-suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3receptors.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1332033</pmid><doi>10.1073/pnas.89.21.10178</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1992-11, Vol.89 (21), p.10178-10182 |
| issn | 0027-8424 1091-6490 |
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| subjects | 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology Agonists Animals Antisense Elements (Genetics) Base Sequence Biological and medical sciences Blotting, Southern Bromocriptine - pharmacology Central nervous system characterization Complementary DNA Deoxyribonucleic acid DNA DNA - genetics DNA - isolation & purification dopamine Dopamine receptors Electric potential Electrophysiology Ergolines - pharmacology Evoked Potentials - drug effects Fundamental and applied biological sciences. Psychology Gels Medical research Messenger RNA Microscopy, Fluorescence Molecular Sequence Data neostriatum Neostriatum - cytology Neostriatum - physiology Neurology Neurons Neurons - cytology Neurons - physiology Neuroscience Oligodeoxyribonucleotides Polymerase chain reaction Quinpirole Rats Receptors Receptors, Dopamine - analysis Receptors, Dopamine - genetics Receptors, Dopamine - physiology Receptors, Dopamine D1 - analysis Receptors, Dopamine D1 - genetics Receptors, Dopamine D1 - physiology Receptors, Dopamine D2 - analysis Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - physiology Receptors, Dopamine D3 Ribonucleic acid RNA RNA Probes RNA, Messenger - genetics RNA, Messenger - isolation & purification Sodium Channels - drug effects Sodium Channels - physiology substantia nigra Substantia Nigra - cytology Substantia Nigra - physiology Vertebrates: nervous system and sense organs |
| title | Dopamine Receptor Subtypes Colocalize in Rat Striatonigral Neurons |
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