Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors
Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ 1 R) mediates c...
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| Veröffentlicht in: | Molecular neurobiology 2019-02, Vol.56 (2), p.1196-1210 |
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| creator | Aguinaga, David Medrano, Mireia Cordomí, Arnau Jiménez-Rosés, Mireia Angelats, Edgar Casanovas, Mireia Vega-Quiroga, Ignacio Canela, Enric I. Petrovic, Milos Gysling, Katia Pardo, Leonardo Franco, Rafael Navarro, Gemma |
| description | Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ
1
R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ
1
R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ
1
R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ
1
R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors. |
| doi_str_mv | 10.1007/s12035-018-1140-7 |
| format | Article |
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1
R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ
1
R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ
1
R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ
1
R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-018-1140-7</identifier><identifier>PMID: 29876881</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Addictions ; Animals ; Anorexia ; Biomedical and Life Sciences ; Biomedicine ; Calcium ; Calcium - metabolism ; Cell Biology ; Cell surface ; Cells, Cultured ; Cocaine ; Cocaine - pharmacology ; Corpus Striatum - cytology ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Dopamine Uptake Inhibitors - pharmacology ; Eating disorders ; Ghrelin ; Ghrelin - metabolism ; HEK293 Cells ; Humans ; Hunger ; Macromolecules ; Male ; Models, Molecular ; Neurobiology ; Neurology ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Neurosciences ; Oleanolic Acid - analogs & derivatives ; Oleanolic Acid - metabolism ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptors, sigma - metabolism ; Reinforcement ; Saponins - metabolism ; Sigma-1 Receptor ; Signal Transduction - drug effects</subject><ispartof>Molecular neurobiology, 2019-02, Vol.56 (2), p.1196-1210</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Molecular Neurobiology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-dfdd88071354dffb1bc5e3a8193417681b66d9bda6f122c95145a0b96d71cdeb3</citedby><cites>FETCH-LOGICAL-c415t-dfdd88071354dffb1bc5e3a8193417681b66d9bda6f122c95145a0b96d71cdeb3</cites><orcidid>0000-0003-2549-4919</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-018-1140-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-018-1140-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29876881$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aguinaga, David</creatorcontrib><creatorcontrib>Medrano, Mireia</creatorcontrib><creatorcontrib>Cordomí, Arnau</creatorcontrib><creatorcontrib>Jiménez-Rosés, Mireia</creatorcontrib><creatorcontrib>Angelats, Edgar</creatorcontrib><creatorcontrib>Casanovas, Mireia</creatorcontrib><creatorcontrib>Vega-Quiroga, Ignacio</creatorcontrib><creatorcontrib>Canela, Enric I.</creatorcontrib><creatorcontrib>Petrovic, Milos</creatorcontrib><creatorcontrib>Gysling, Katia</creatorcontrib><creatorcontrib>Pardo, Leonardo</creatorcontrib><creatorcontrib>Franco, Rafael</creatorcontrib><creatorcontrib>Navarro, Gemma</creatorcontrib><title>Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ
1
R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ
1
R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ
1
R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ
1
R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors.</description><subject>Addictions</subject><subject>Animals</subject><subject>Anorexia</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Cell Biology</subject><subject>Cell surface</subject><subject>Cells, Cultured</subject><subject>Cocaine</subject><subject>Cocaine - pharmacology</subject><subject>Corpus Striatum - cytology</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Eating disorders</subject><subject>Ghrelin</subject><subject>Ghrelin - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Hunger</subject><subject>Macromolecules</subject><subject>Male</subject><subject>Models, Molecular</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurosciences</subject><subject>Oleanolic Acid - analogs & derivatives</subject><subject>Oleanolic Acid - metabolism</subject><subject>Phosphorylation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, sigma - metabolism</subject><subject>Reinforcement</subject><subject>Saponins - metabolism</subject><subject>Sigma-1 Receptor</subject><subject>Signal Transduction - drug effects</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1P3DAQhq2qqCwfP6CXylIvHAj1OHHsHNsVsCshkMrH1XLsMYQm8dZOhPj3ZNkFpEo9jUbzzDuv5iXkK7ATYEz-SMBZLjIGKgMoWCY_kRkIUU2d4p_JjKkqz2RZqF2yl9IjY5wDk1_ILq-ULJWCGannwZqmR_qrDfZPoqfeox0SDZ4uxv4eI12E2IUej-n5Q8S26Y_pXWPosh8wGjs0oadPzfBAL3GMoTctvW7uO5MB_Y0WV0OI6YDseNMmPNzWfXJ7dnozX2QXV-fL-c-LzBYghsx555RiEnJROO9rqK3A3Cio8gImt1CXpatqZ0oPnNtKQCEMq6vSSbAO63yfHG10VzH8HTENumuSxbY1PYYxac4ElEIWlZrQ7_-gj2GMk_tXismSy0JOFGwoG0NKEb1exaYz8VkD0-sA9CYAPQWg1wHo9c63rfJYd-jeN94-PgF8A6RptH7wx-n_q74ArnCPPg</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Aguinaga, David</creator><creator>Medrano, Mireia</creator><creator>Cordomí, Arnau</creator><creator>Jiménez-Rosés, Mireia</creator><creator>Angelats, Edgar</creator><creator>Casanovas, Mireia</creator><creator>Vega-Quiroga, Ignacio</creator><creator>Canela, Enric I.</creator><creator>Petrovic, Milos</creator><creator>Gysling, Katia</creator><creator>Pardo, Leonardo</creator><creator>Franco, Rafael</creator><creator>Navarro, Gemma</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2549-4919</orcidid></search><sort><creationdate>20190201</creationdate><title>Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors</title><author>Aguinaga, David ; Medrano, Mireia ; Cordomí, Arnau ; Jiménez-Rosés, Mireia ; Angelats, Edgar ; Casanovas, Mireia ; Vega-Quiroga, Ignacio ; Canela, Enric I. ; Petrovic, Milos ; Gysling, Katia ; Pardo, Leonardo ; Franco, Rafael ; Navarro, Gemma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-dfdd88071354dffb1bc5e3a8193417681b66d9bda6f122c95145a0b96d71cdeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Addictions</topic><topic>Animals</topic><topic>Anorexia</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Cell Biology</topic><topic>Cell surface</topic><topic>Cells, Cultured</topic><topic>Cocaine</topic><topic>Cocaine - pharmacology</topic><topic>Corpus Striatum - cytology</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Eating disorders</topic><topic>Ghrelin</topic><topic>Ghrelin - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Hunger</topic><topic>Macromolecules</topic><topic>Male</topic><topic>Models, Molecular</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurosciences</topic><topic>Oleanolic Acid - analogs & derivatives</topic><topic>Oleanolic Acid - metabolism</topic><topic>Phosphorylation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, sigma - metabolism</topic><topic>Reinforcement</topic><topic>Saponins - 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Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aguinaga, David</au><au>Medrano, Mireia</au><au>Cordomí, Arnau</au><au>Jiménez-Rosés, Mireia</au><au>Angelats, Edgar</au><au>Casanovas, Mireia</au><au>Vega-Quiroga, Ignacio</au><au>Canela, Enric I.</au><au>Petrovic, Milos</au><au>Gysling, Katia</au><au>Pardo, Leonardo</au><au>Franco, Rafael</au><au>Navarro, Gemma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>56</volume><issue>2</issue><spage>1196</spage><epage>1210</epage><pages>1196-1210</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ
1
R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ
1
R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ
1
R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ
1
R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29876881</pmid><doi>10.1007/s12035-018-1140-7</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-2549-4919</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 0893-7648 1559-1182 |
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| subjects | Addictions Animals Anorexia Biomedical and Life Sciences Biomedicine Calcium Calcium - metabolism Cell Biology Cell surface Cells, Cultured Cocaine Cocaine - pharmacology Corpus Striatum - cytology Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine Uptake Inhibitors - pharmacology Eating disorders Ghrelin Ghrelin - metabolism HEK293 Cells Humans Hunger Macromolecules Male Models, Molecular Neurobiology Neurology Neurons - cytology Neurons - drug effects Neurons - metabolism Neurosciences Oleanolic Acid - analogs & derivatives Oleanolic Acid - metabolism Phosphorylation Rats Rats, Sprague-Dawley Receptors, sigma - metabolism Reinforcement Saponins - metabolism Sigma-1 Receptor Signal Transduction - drug effects |
| title | Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors |
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