Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor
A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC 132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opi...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 1995-11, Vol.270 (5237), p.792-794 |
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creator | Reinscheid, Rainer K. Nothacker, Hans-Peter Bourson, Anne Ardati, Ali Henningsen, Robert A. Bunzow, James R. Grandy, David K. Langen, Hanno Monsma, Frederick J. Civelli, Olivier |
description | A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC 132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior. |
doi_str_mv | 10.1126/science.270.5237.792 |
format | Article |
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This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.270.5237.792</identifier><identifier>PMID: 7481766</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Adenylyl Cyclase Inhibitors ; Amino Acid Sequence ; Analgesics - pharmacology ; Animals ; Biochemistry and metabolism ; Biological and medical sciences ; Central nervous system ; CHO Cells ; Colforsin - pharmacology ; Cricetinae ; Dosage ; Fundamental and applied biological sciences. Psychology ; G proteins ; GTP-Binding Proteins - metabolism ; Hypothalamus - chemistry ; Injections, Intraventricular ; Injections, Spinal ; Ligands ; Mice ; Molecular Sequence Data ; Motor Activity - drug effects ; Neuropeptides ; Nociceptin ; Opioid peptides ; Opioid Peptides - chemistry ; Opioid Peptides - isolation & purification ; Opioid Peptides - metabolism ; Opioid Peptides - pharmacology ; Opioid receptors ; Opioids ; Orphans ; Pain Measurement ; Receptors ; Receptors, Neuropeptide - metabolism ; Receptors, Opioid - metabolism ; String theory ; Swine ; Transfection ; Vertebrates: nervous system and sense organs</subject><ispartof>Science (American Association for the Advancement of Science), 1995-11, Vol.270 (5237), p.792-794</ispartof><rights>Copyright 1995 American Association for the Advancement of Science</rights><rights>1996 INIST-CNRS</rights><rights>COPYRIGHT 1995 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1995 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c572t-2268ec3c6aa9dc0830307654acdca372ba93efb09a1f8685f3fbe37b2a057df53</citedby><cites>FETCH-LOGICAL-c572t-2268ec3c6aa9dc0830307654acdca372ba93efb09a1f8685f3fbe37b2a057df53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2888925$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2888925$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2919155$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7481766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reinscheid, Rainer K.</creatorcontrib><creatorcontrib>Nothacker, Hans-Peter</creatorcontrib><creatorcontrib>Bourson, Anne</creatorcontrib><creatorcontrib>Ardati, Ali</creatorcontrib><creatorcontrib>Henningsen, Robert A.</creatorcontrib><creatorcontrib>Bunzow, James R.</creatorcontrib><creatorcontrib>Grandy, David K.</creatorcontrib><creatorcontrib>Langen, Hanno</creatorcontrib><creatorcontrib>Monsma, Frederick J.</creatorcontrib><creatorcontrib>Civelli, Olivier</creatorcontrib><title>Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC 132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.</description><subject>Adenylyl Cyclase Inhibitors</subject><subject>Amino Acid Sequence</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Central nervous system</subject><subject>CHO Cells</subject><subject>Colforsin - pharmacology</subject><subject>Cricetinae</subject><subject>Dosage</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>G proteins</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Hypothalamus - chemistry</subject><subject>Injections, Intraventricular</subject><subject>Injections, Spinal</subject><subject>Ligands</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Motor Activity - drug effects</subject><subject>Neuropeptides</subject><subject>Nociceptin</subject><subject>Opioid peptides</subject><subject>Opioid Peptides - chemistry</subject><subject>Opioid Peptides - isolation & purification</subject><subject>Opioid Peptides - metabolism</subject><subject>Opioid Peptides - pharmacology</subject><subject>Opioid receptors</subject><subject>Opioids</subject><subject>Orphans</subject><subject>Pain Measurement</subject><subject>Receptors</subject><subject>Receptors, Neuropeptide - metabolism</subject><subject>Receptors, Opioid - metabolism</subject><subject>String theory</subject><subject>Swine</subject><subject>Transfection</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0k9v0zAYBvAIgUYZfIMh5YAQh6X4Tx3b3ErFyqRqBQZcLcd503mkcbAdBN8eV42GKlWi8sGSn9_ry_tk2QVGU4xJ-TYYC52BKeFoygjlUy7Jo2yCkWSFJIg-ziYI0bIQiLOn2bMQ7hFKmaRn2RmfCczLcpLdrn1_pzvb5Vef3-Xz_AYG73roo60hj3c65nMT7S8dIeS6y9e9dbZu7Q_Il_kn7yLYrli4oW-hzr-ASYPOP8-eNLoN8GK8z7NvVx--Lj4Wq_XyejFfFYZxEgtCSgGGmlJrWRskKKKIl2ymTW005aTSkkJTIalxI0rBGtpUQHlFNGK8bhg9z17v_-29-zlAiGprg4G21R24ISiefkNIkP9CzBHGgsgEL_dwo1tQtmtc9NpsoAOvW9dBY9PzHHMmyKycJV4c4enUsLXmmH9z4BOJ8Dtu9BCCur69OZmuv59M3y9PpWK5OqCXx6hxbQsbUGmRi_UBn-258S4ED43qvd1q_0dhpHZ1VWNdVaqr2tVVpbqmsZfjZoZqC_XD0NjPlL8acx2MbhuvO2PDAyMSS8x2TbjYs_uQ-vcvFkJIwuhfG_H4iA</recordid><startdate>19951103</startdate><enddate>19951103</enddate><creator>Reinscheid, Rainer K.</creator><creator>Nothacker, Hans-Peter</creator><creator>Bourson, Anne</creator><creator>Ardati, Ali</creator><creator>Henningsen, Robert A.</creator><creator>Bunzow, James R.</creator><creator>Grandy, David K.</creator><creator>Langen, Hanno</creator><creator>Monsma, Frederick J.</creator><creator>Civelli, Olivier</creator><general>American Society for the Advancement of Science</general><general>American Association for the Advancement of Science</general><scope>IQODW</scope><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>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19951103</creationdate><title>Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor</title><author>Reinscheid, Rainer K. ; Nothacker, Hans-Peter ; Bourson, Anne ; Ardati, Ali ; Henningsen, Robert A. ; Bunzow, James R. ; Grandy, David K. ; Langen, Hanno ; Monsma, Frederick J. ; Civelli, Olivier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-2268ec3c6aa9dc0830307654acdca372ba93efb09a1f8685f3fbe37b2a057df53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Adenylyl Cyclase Inhibitors</topic><topic>Amino Acid Sequence</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Central nervous system</topic><topic>CHO Cells</topic><topic>Colforsin - pharmacology</topic><topic>Cricetinae</topic><topic>Dosage</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>G proteins</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Hypothalamus - chemistry</topic><topic>Injections, Intraventricular</topic><topic>Injections, Spinal</topic><topic>Ligands</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Motor Activity - drug effects</topic><topic>Neuropeptides</topic><topic>Nociceptin</topic><topic>Opioid peptides</topic><topic>Opioid Peptides - chemistry</topic><topic>Opioid Peptides - isolation & purification</topic><topic>Opioid Peptides - metabolism</topic><topic>Opioid Peptides - pharmacology</topic><topic>Opioid receptors</topic><topic>Opioids</topic><topic>Orphans</topic><topic>Pain Measurement</topic><topic>Receptors</topic><topic>Receptors, Neuropeptide - metabolism</topic><topic>Receptors, Opioid - metabolism</topic><topic>String theory</topic><topic>Swine</topic><topic>Transfection</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reinscheid, Rainer K.</creatorcontrib><creatorcontrib>Nothacker, Hans-Peter</creatorcontrib><creatorcontrib>Bourson, Anne</creatorcontrib><creatorcontrib>Ardati, Ali</creatorcontrib><creatorcontrib>Henningsen, Robert A.</creatorcontrib><creatorcontrib>Bunzow, James R.</creatorcontrib><creatorcontrib>Grandy, David K.</creatorcontrib><creatorcontrib>Langen, Hanno</creatorcontrib><creatorcontrib>Monsma, Frederick J.</creatorcontrib><creatorcontrib>Civelli, Olivier</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>Gale In Context: Biography</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reinscheid, Rainer K.</au><au>Nothacker, Hans-Peter</au><au>Bourson, Anne</au><au>Ardati, Ali</au><au>Henningsen, Robert A.</au><au>Bunzow, James R.</au><au>Grandy, David K.</au><au>Langen, Hanno</au><au>Monsma, Frederick J.</au><au>Civelli, Olivier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>1995-11-03</date><risdate>1995</risdate><volume>270</volume><issue>5237</issue><spage>792</spage><epage>794</epage><pages>792-794</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC 132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>7481766</pmid><doi>10.1126/science.270.5237.792</doi><tpages>3</tpages></addata></record> |
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source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
subjects | Adenylyl Cyclase Inhibitors Amino Acid Sequence Analgesics - pharmacology Animals Biochemistry and metabolism Biological and medical sciences Central nervous system CHO Cells Colforsin - pharmacology Cricetinae Dosage Fundamental and applied biological sciences. Psychology G proteins GTP-Binding Proteins - metabolism Hypothalamus - chemistry Injections, Intraventricular Injections, Spinal Ligands Mice Molecular Sequence Data Motor Activity - drug effects Neuropeptides Nociceptin Opioid peptides Opioid Peptides - chemistry Opioid Peptides - isolation & purification Opioid Peptides - metabolism Opioid Peptides - pharmacology Opioid receptors Opioids Orphans Pain Measurement Receptors Receptors, Neuropeptide - metabolism Receptors, Opioid - metabolism String theory Swine Transfection Vertebrates: nervous system and sense organs |
title | Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor |
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