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Identification of the Receptor Subtype Involved in the Analgesic Effect of Neurotensin
The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity...
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| Published in: | The Journal of neuroscience 1999-01, Vol.19 (1), p.503-510 |
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| Main Authors: | , , , , , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c539t-19a496ebcc6acc7687814a032fb3496bf029e25c0f8bbc4fd37cb5cc990d0ded3 |
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| cites | cdi_FETCH-LOGICAL-c539t-19a496ebcc6acc7687814a032fb3496bf029e25c0f8bbc4fd37cb5cc990d0ded3 |
| container_end_page | 510 |
| container_issue | 1 |
| container_start_page | 503 |
| container_title | The Journal of neuroscience |
| container_volume | 19 |
| creator | Dubuc, Isabelle Sarret, Philippe Labbe-Jullie, Catherine Botto, Jean-Marie Honore, Eric Bourdel, Elisabeth Martinez, Jean Costentin, Jean Vincent, Jean-Pierre Kitabgi, Patrick Mazella, Jean |
| description | The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia. |
| doi_str_mv | 10.1523/jneurosci.19-01-00503.1999 |
| format | article |
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Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/jneurosci.19-01-00503.1999</identifier><identifier>PMID: 9870978</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Analgesics - pharmacology ; Analysis of Variance ; Animals ; Body Temperature Regulation - drug effects ; CHO Cells ; Cricetinae ; Injections, Intraventricular ; Male ; Mice ; Neurotensin - metabolism ; Neurotensin - pharmacology ; Oligodeoxyribonucleotides, Antisense ; Receptors, Neurotensin - drug effects ; Receptors, Neurotensin - metabolism ; RNA, Messenger - biosynthesis ; Structure-Activity Relationship</subject><ispartof>The Journal of neuroscience, 1999-01, Vol.19 (1), p.503-510</ispartof><rights>Copyright © 1999 Society for Neuroscience 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-19a496ebcc6acc7687814a032fb3496bf029e25c0f8bbc4fd37cb5cc990d0ded3</citedby><cites>FETCH-LOGICAL-c539t-19a496ebcc6acc7687814a032fb3496bf029e25c0f8bbc4fd37cb5cc990d0ded3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782393/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782393/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9870978$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dubuc, Isabelle</creatorcontrib><creatorcontrib>Sarret, Philippe</creatorcontrib><creatorcontrib>Labbe-Jullie, Catherine</creatorcontrib><creatorcontrib>Botto, Jean-Marie</creatorcontrib><creatorcontrib>Honore, Eric</creatorcontrib><creatorcontrib>Bourdel, Elisabeth</creatorcontrib><creatorcontrib>Martinez, Jean</creatorcontrib><creatorcontrib>Costentin, Jean</creatorcontrib><creatorcontrib>Vincent, Jean-Pierre</creatorcontrib><creatorcontrib>Kitabgi, Patrick</creatorcontrib><creatorcontrib>Mazella, Jean</creatorcontrib><title>Identification of the Receptor Subtype Involved in the Analgesic Effect of Neurotensin</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.</description><subject>Analgesics - pharmacology</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Body Temperature Regulation - drug effects</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Injections, Intraventricular</subject><subject>Male</subject><subject>Mice</subject><subject>Neurotensin - metabolism</subject><subject>Neurotensin - pharmacology</subject><subject>Oligodeoxyribonucleotides, Antisense</subject><subject>Receptors, Neurotensin - drug effects</subject><subject>Receptors, Neurotensin - metabolism</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Structure-Activity Relationship</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNqFkVFr2zAUhcXY6LJuP2FgBtubuyvLtqw9DErI2pTSQrvuVcjyVaLiSKklJ_TfT2lCaZ_6dC-c7xzu5RDyjcIJrQr2897hOPig7QkVOdAcoAKWdiHekUkiRF6UQN-TCRQc8rrk5UfyKYR7AOBA-RE5Eg0HwZsJ-Tfv0EVrrFbRepd5k8UlZjeocR39kN2ObXxcYzZ3G99vsMusewJOneoXGKzOZsagjjvj1e6qiC5Y95l8MKoP-OUwj8ndn9nf6Xl-eX02n55e5rpiIuZUqFLU2GpdK6153fCGlgpYYVqWhNZAIbCoNJimbXVpOsZ1W2ktBHTQYceOye997npsV9jp9Mugerke7EoNj9IrK18rzi7lwm9kzZuCCZYCfhwCBv8wYohyZYPGvlcO_RhkLaqKNlX9Jkg5LRkrRAJ_7UGdKgoDmudrKMhdffLianZ3c307nUsqJFD5VJ_c1ZfMX1_-82w99JX073t9aRfLrR1QhpXq-0RTud1uUx6VKYz9Bz-5qFo</recordid><startdate>19990101</startdate><enddate>19990101</enddate><creator>Dubuc, Isabelle</creator><creator>Sarret, Philippe</creator><creator>Labbe-Jullie, Catherine</creator><creator>Botto, Jean-Marie</creator><creator>Honore, Eric</creator><creator>Bourdel, Elisabeth</creator><creator>Martinez, Jean</creator><creator>Costentin, Jean</creator><creator>Vincent, Jean-Pierre</creator><creator>Kitabgi, Patrick</creator><creator>Mazella, Jean</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990101</creationdate><title>Identification of the Receptor Subtype Involved in the Analgesic Effect of Neurotensin</title><author>Dubuc, Isabelle ; Sarret, Philippe ; Labbe-Jullie, Catherine ; Botto, Jean-Marie ; Honore, Eric ; Bourdel, Elisabeth ; Martinez, Jean ; Costentin, Jean ; Vincent, Jean-Pierre ; Kitabgi, Patrick ; Mazella, Jean</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-19a496ebcc6acc7687814a032fb3496bf029e25c0f8bbc4fd37cb5cc990d0ded3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Analgesics - pharmacology</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Body Temperature Regulation - drug effects</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Injections, Intraventricular</topic><topic>Male</topic><topic>Mice</topic><topic>Neurotensin - metabolism</topic><topic>Neurotensin - pharmacology</topic><topic>Oligodeoxyribonucleotides, Antisense</topic><topic>Receptors, Neurotensin - drug effects</topic><topic>Receptors, Neurotensin - metabolism</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dubuc, Isabelle</creatorcontrib><creatorcontrib>Sarret, Philippe</creatorcontrib><creatorcontrib>Labbe-Jullie, Catherine</creatorcontrib><creatorcontrib>Botto, Jean-Marie</creatorcontrib><creatorcontrib>Honore, Eric</creatorcontrib><creatorcontrib>Bourdel, Elisabeth</creatorcontrib><creatorcontrib>Martinez, Jean</creatorcontrib><creatorcontrib>Costentin, Jean</creatorcontrib><creatorcontrib>Vincent, Jean-Pierre</creatorcontrib><creatorcontrib>Kitabgi, Patrick</creatorcontrib><creatorcontrib>Mazella, Jean</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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dubuc, Isabelle</au><au>Sarret, Philippe</au><au>Labbe-Jullie, Catherine</au><au>Botto, Jean-Marie</au><au>Honore, Eric</au><au>Bourdel, Elisabeth</au><au>Martinez, Jean</au><au>Costentin, Jean</au><au>Vincent, Jean-Pierre</au><au>Kitabgi, Patrick</au><au>Mazella, Jean</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of the Receptor Subtype Involved in the Analgesic Effect of Neurotensin</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>1999-01-01</date><risdate>1999</risdate><volume>19</volume><issue>1</issue><spage>503</spage><epage>510</epage><pages>503-510</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. 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| identifier | ISSN: 0270-6474 |
| ispartof | The Journal of neuroscience, 1999-01, Vol.19 (1), p.503-510 |
| issn | 0270-6474 1529-2401 |
| language | eng |
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| source | Open Access: PubMed Central |
| subjects | Analgesics - pharmacology Analysis of Variance Animals Body Temperature Regulation - drug effects CHO Cells Cricetinae Injections, Intraventricular Male Mice Neurotensin - metabolism Neurotensin - pharmacology Oligodeoxyribonucleotides, Antisense Receptors, Neurotensin - drug effects Receptors, Neurotensin - metabolism RNA, Messenger - biosynthesis Structure-Activity Relationship |
| title | Identification of the Receptor Subtype Involved in the Analgesic Effect of Neurotensin |
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