D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum
We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that acti...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2007-01, Vol.104 (2), p.654-659 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Rashid, Asim J So, Christopher H Kong, Michael M.C Furtak, Teresa El-Ghundi, Mufida Cheng, Regina O'Dowd, Brian F George, Susan R |
| description | We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated Gq/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1-D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1-D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIα in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity. |
| doi_str_mv | 10.1073/pnas.0604049104 |
| format | Article |
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The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated Gq/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1-D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1-D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIα in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0604049104</identifier><identifier>PMID: 17194762</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological Sciences ; Brain ; Cell Line ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Dopamine Agonists - pharmacology ; Dopamine Antagonists - pharmacology ; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism ; Humans ; Kinases ; Male ; Mice ; Mice, Knockout ; Neurotransmitters ; Protein Structure, Quaternary ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D1 - chemistry ; Receptors, Dopamine D1 - deficiency ; Receptors, Dopamine D1 - genetics ; Receptors, Dopamine D1 - metabolism ; Receptors, Dopamine D2 - chemistry ; Receptors, Dopamine D2 - deficiency ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - metabolism ; Signal Transduction</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2007-01, Vol.104 (2), p.654-659</ispartof><rights>Copyright National Academy of Sciences Jan 9, 2007</rights><rights>2006 by The National Academy of Sciences of the USA 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329t-37ae527cabaf3674537d5ea32480043ddf39d3abe33ed6f540f1ec68a907dbbe3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/104/2.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766439/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766439/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17194762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rashid, Asim J</creatorcontrib><creatorcontrib>So, Christopher H</creatorcontrib><creatorcontrib>Kong, Michael M.C</creatorcontrib><creatorcontrib>Furtak, Teresa</creatorcontrib><creatorcontrib>El-Ghundi, Mufida</creatorcontrib><creatorcontrib>Cheng, Regina</creatorcontrib><creatorcontrib>O'Dowd, Brian F</creatorcontrib><creatorcontrib>George, Susan R</creatorcontrib><title>D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. 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Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIα in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity.</description><subject>Animals</subject><subject>Biological Sciences</subject><subject>Brain</subject><subject>Cell Line</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Dopamine Agonists - pharmacology</subject><subject>Dopamine Antagonists - pharmacology</subject><subject>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurotransmitters</subject><subject>Protein Structure, Quaternary</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Dopamine D1 - chemistry</subject><subject>Receptors, Dopamine D1 - deficiency</subject><subject>Receptors, Dopamine D1 - genetics</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Receptors, Dopamine D2 - chemistry</subject><subject>Receptors, Dopamine D2 - deficiency</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Signal Transduction</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptks1v1DAQxSMEotvCmRNg9cAt7fgjzvpSCbVQkCpxgJ6t2WSycZXEqe0U9r_H0AUK4jTSvJ_evNFMUbzgcMKhlqfzhPEENChQhoN6VKw4GF5qZeBxsQIQdblWQh0UhzHeAICp1vC0OOA1N6rWYlXsLnh5IVjrZxzdRCxQQ3PygfWUKHg_uK0fKUT21aWeLZO7XYjNPYYRGz_47Y5hINb4ZR6oZcmzgLNrGTbJ3WFyfmK-Y5e3p5wzN7HUE4spOEzL-Kx40uEQ6fm-HhXX7999Of9QXn26_Hj-9qpspDCplDVSJeoGN9hJXatK1m1FKIVaAyjZtp00rcQNSUmt7ioFHadGr9FA3W5y-6g4u_edl81IbUNTCjjYObgRw856dPZvZXK93fo7y2utlTTZ4M3eIPi8fUx2dLGhYcCJ_BKtXisuQVYZPP4HvPFLmPJyVsAPRBiZoVcP4_zO8eskGXi5B_Jt_8igrLC6Ug_i_Fe33TIMib6lDL6-Bzv0FrfBRXv9-WeQ_Dl5mpHfAfLdsO0</recordid><startdate>20070109</startdate><enddate>20070109</enddate><creator>Rashid, Asim J</creator><creator>So, Christopher H</creator><creator>Kong, Michael M.C</creator><creator>Furtak, Teresa</creator><creator>El-Ghundi, Mufida</creator><creator>Cheng, Regina</creator><creator>O'Dowd, Brian F</creator><creator>George, Susan R</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070109</creationdate><title>D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum</title><author>Rashid, Asim J ; So, Christopher H ; Kong, Michael M.C ; Furtak, Teresa ; El-Ghundi, Mufida ; Cheng, Regina ; O'Dowd, Brian F ; George, Susan R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-37ae527cabaf3674537d5ea32480043ddf39d3abe33ed6f540f1ec68a907dbbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Biological Sciences</topic><topic>Brain</topic><topic>Cell Line</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Dopamine Agonists - pharmacology</topic><topic>Dopamine Antagonists - pharmacology</topic><topic>GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neurotransmitters</topic><topic>Protein Structure, Quaternary</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Dopamine D1 - chemistry</topic><topic>Receptors, Dopamine D1 - deficiency</topic><topic>Receptors, Dopamine D1 - genetics</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Receptors, Dopamine D2 - chemistry</topic><topic>Receptors, Dopamine D2 - deficiency</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rashid, Asim J</creatorcontrib><creatorcontrib>So, Christopher H</creatorcontrib><creatorcontrib>Kong, Michael M.C</creatorcontrib><creatorcontrib>Furtak, Teresa</creatorcontrib><creatorcontrib>El-Ghundi, Mufida</creatorcontrib><creatorcontrib>Cheng, Regina</creatorcontrib><creatorcontrib>O'Dowd, Brian F</creatorcontrib><creatorcontrib>George, Susan R</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rashid, Asim J</au><au>So, Christopher H</au><au>Kong, Michael M.C</au><au>Furtak, Teresa</au><au>El-Ghundi, Mufida</au><au>Cheng, Regina</au><au>O'Dowd, Brian F</au><au>George, Susan R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2007-01-09</date><risdate>2007</risdate><volume>104</volume><issue>2</issue><spage>654</spage><epage>659</epage><pages>654-659</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated Gq/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1-D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1-D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIα in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17194762</pmid><doi>10.1073/pnas.0604049104</doi><tpages>6</tpages></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Biological Sciences Brain Cell Line Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine Agonists - pharmacology Dopamine Antagonists - pharmacology GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism Humans Kinases Male Mice Mice, Knockout Neurotransmitters Protein Structure, Quaternary Rats Rats, Sprague-Dawley Receptors, Dopamine D1 - chemistry Receptors, Dopamine D1 - deficiency Receptors, Dopamine D1 - genetics Receptors, Dopamine D1 - metabolism Receptors, Dopamine D2 - chemistry Receptors, Dopamine D2 - deficiency Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism Signal Transduction |
| title | D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum |
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