Modulation of Synaptic Transmission by Nociceptin/Orphanin FQ and Nocistatin in the Spinal Cord Dorsal Horn of Mutant Mice Lacking the Nociceptin/Orphanin FQ Receptor
Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually identified neurons in spinal cord dorsal ho...
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| Veröffentlicht in: | Molecular pharmacology 2001-03, Vol.59 (3), p.612-618 |
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| creator | Ahmadi, S Kotalla, C Gühring, H Takeshima, H Pahl, A Zeilhofer, H U |
| description | Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit
opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually
identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor
(N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and γ-aminobutyric
acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent
manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not α-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely
absent in N/OFQ-R receptor-deficient (N/OFQ-R â/â ) mice and significantly reduced in heterozygous (N/OFQ-R +/â ) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these
results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an
animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive
effects in N/OFQ-R â/â mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its
spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor. |
| doi_str_mv | 10.1124/mol.59.3.612 |
| format | Article |
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opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually
identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor
(N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and γ-aminobutyric
acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent
manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not α-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely
absent in N/OFQ-R receptor-deficient (N/OFQ-R â/â ) mice and significantly reduced in heterozygous (N/OFQ-R +/â ) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these
results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an
animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive
effects in N/OFQ-R â/â mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its
spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>DOI: 10.1124/mol.59.3.612</identifier><identifier>PMID: 11179457</identifier><language>eng</language><publisher>United States: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Analgesics, Opioid - pharmacology ; Animals ; Excitatory Postsynaptic Potentials - drug effects ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Nociceptin ; Nociceptin Receptor ; Opioid Peptides - pharmacology ; Pain Measurement - drug effects ; Posterior Horn Cells - drug effects ; Posterior Horn Cells - physiology ; Receptors, Glutamate - drug effects ; Receptors, Glutamate - physiology ; Receptors, Opioid - deficiency ; Receptors, Opioid - metabolism ; Spinal Cord ; Synaptic Transmission - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>Molecular pharmacology, 2001-03, Vol.59 (3), p.612-618</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-961ecb815da2b32a05795788f1c8f063fe7c748e8d0f8a4fb9b1d6b028d056083</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11179457$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmadi, S</creatorcontrib><creatorcontrib>Kotalla, C</creatorcontrib><creatorcontrib>Gühring, H</creatorcontrib><creatorcontrib>Takeshima, H</creatorcontrib><creatorcontrib>Pahl, A</creatorcontrib><creatorcontrib>Zeilhofer, H U</creatorcontrib><title>Modulation of Synaptic Transmission by Nociceptin/Orphanin FQ and Nocistatin in the Spinal Cord Dorsal Horn of Mutant Mice Lacking the Nociceptin/Orphanin FQ Receptor</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit
opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually
identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor
(N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and γ-aminobutyric
acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent
manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not α-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely
absent in N/OFQ-R receptor-deficient (N/OFQ-R â/â ) mice and significantly reduced in heterozygous (N/OFQ-R +/â ) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these
results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an
animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive
effects in N/OFQ-R â/â mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its
spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor.</description><subject>Analgesics, Opioid - pharmacology</subject><subject>Animals</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Female</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mutation</subject><subject>Nociceptin</subject><subject>Nociceptin Receptor</subject><subject>Opioid Peptides - pharmacology</subject><subject>Pain Measurement - drug effects</subject><subject>Posterior Horn Cells - drug effects</subject><subject>Posterior Horn Cells - physiology</subject><subject>Receptors, Glutamate - drug effects</subject><subject>Receptors, Glutamate - physiology</subject><subject>Receptors, Opioid - deficiency</subject><subject>Receptors, Opioid - metabolism</subject><subject>Spinal Cord</subject><subject>Synaptic Transmission - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1PwyAch4nR6Hy5eTZc9GQn0NLSo5mvyeai08QboZRuaAsV2ph9IT-n7CXxZEIC-f8eHhJ-AJxiNMSYJFeNrYc0H8bDFJMdMMCU4AhhjHfBACGSRiyn7wfg0PsPhHBCGdoHByHO8oRmA_AzsWVfi05bA20FZ0sj2k5L-OqE8Y32fhUUS_hkpZYqROZq6tqFMNrAu2coTLmOfBcUBobVLRSctdqIGo6sK-GNdT6cH6xbPzDpO2E6OAkyOBbyU5v5-so__he1Glp3DPYqUXt1st2PwNvd7evoIRpP7x9H1-NIJgR3UZ5iJQuGaSlIEROBaJbTjLEKS1ahNK5UJrOEKVaiiomkKvICl2mBSBjQFLH4CFxsvK2zX73yHQ9_IFVdC6Ns73mGUhJnMQng5QaUznrvVMVbpxvhlhwjvuqFh144zXnMQy8BP9t6-6JR5R-8LSIA5xtgoeeLb-0UD5_gGiFtbefLP9EvLdaYWw</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>Ahmadi, S</creator><creator>Kotalla, C</creator><creator>Gühring, H</creator><creator>Takeshima, H</creator><creator>Pahl, A</creator><creator>Zeilhofer, H U</creator><general>American Society for Pharmacology and Experimental Therapeutics</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>7X8</scope></search><sort><creationdate>20010301</creationdate><title>Modulation of Synaptic Transmission by Nociceptin/Orphanin FQ and Nocistatin in the Spinal Cord Dorsal Horn of Mutant Mice Lacking the Nociceptin/Orphanin FQ Receptor</title><author>Ahmadi, S ; Kotalla, C ; Gühring, H ; Takeshima, H ; Pahl, A ; Zeilhofer, H U</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-961ecb815da2b32a05795788f1c8f063fe7c748e8d0f8a4fb9b1d6b028d056083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Analgesics, Opioid - pharmacology</topic><topic>Animals</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Female</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mutation</topic><topic>Nociceptin</topic><topic>Nociceptin Receptor</topic><topic>Opioid Peptides - pharmacology</topic><topic>Pain Measurement - drug effects</topic><topic>Posterior Horn Cells - drug effects</topic><topic>Posterior Horn Cells - physiology</topic><topic>Receptors, Glutamate - drug effects</topic><topic>Receptors, Glutamate - physiology</topic><topic>Receptors, Opioid - deficiency</topic><topic>Receptors, Opioid - metabolism</topic><topic>Spinal Cord</topic><topic>Synaptic Transmission - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmadi, S</creatorcontrib><creatorcontrib>Kotalla, C</creatorcontrib><creatorcontrib>Gühring, H</creatorcontrib><creatorcontrib>Takeshima, H</creatorcontrib><creatorcontrib>Pahl, A</creatorcontrib><creatorcontrib>Zeilhofer, H U</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahmadi, S</au><au>Kotalla, C</au><au>Gühring, H</au><au>Takeshima, H</au><au>Pahl, A</au><au>Zeilhofer, H U</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of Synaptic Transmission by Nociceptin/Orphanin FQ and Nocistatin in the Spinal Cord Dorsal Horn of Mutant Mice Lacking the Nociceptin/Orphanin FQ Receptor</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>59</volume><issue>3</issue><spage>612</spage><epage>618</epage><pages>612-618</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><abstract>Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two neuropeptides derived from the same precursor protein that exhibit
opposing effects on spinal neurotransmission and nociception. Here, we have used whole-cell, patch-clamp recordings from visually
identified neurons in spinal cord dorsal horn slices of genetically modified mice to investigate the role of the N/OFQ receptor
(N/OFQ-R) in the modulatory action of both peptides on excitatory glutamatergic and inhibitory glycinergic and γ-aminobutyric
acid (GABA)-ergic synaptic transmission. In wild-type mice, N/OFQ selectively suppressed excitatory transmission in a concentration-dependent
manner but left inhibitory synaptic transmission unaffected. In contrast, NST reduced only inhibitory but not α-amino-3-hydroxy-5-methylisoxazole-4-propionic
acid (AMPA) receptor-mediated excitatory synaptic transmission. N/OFQ-mediated inhibition of excitatory transmission was completely
absent in N/OFQ-R receptor-deficient (N/OFQ-R â/â ) mice and significantly reduced in heterozygous (N/OFQ-R +/â ) mice, whereas the action of NST on inhibitory neurotransmission was completely retained. To test for the relevance of these
results for spinal nociception, we investigated the effects of intrathecally injected N/OFQ in the mouse formalin test, an
animal model of tonic pain. N/OFQ (3 nmol/mouse) induced significant antinociception in wild-type mice, but had no antinociceptive
effects in N/OFQ-R â/â mice. These results indicate that the inhibitory action of N/OFQ on excitatory glutamatergic synaptic transmission and its
spinal antinociceptive action are mediated via the N/OFQ receptor, whereas the action of NST is independent of this receptor.</abstract><cop>United States</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>11179457</pmid><doi>10.1124/mol.59.3.612</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular pharmacology, 2001-03, Vol.59 (3), p.612-618 |
| issn | 0026-895X 1521-0111 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Analgesics, Opioid - pharmacology Animals Excitatory Postsynaptic Potentials - drug effects Female Male Mice Mice, Inbred C57BL Mutation Nociceptin Nociceptin Receptor Opioid Peptides - pharmacology Pain Measurement - drug effects Posterior Horn Cells - drug effects Posterior Horn Cells - physiology Receptors, Glutamate - drug effects Receptors, Glutamate - physiology Receptors, Opioid - deficiency Receptors, Opioid - metabolism Spinal Cord Synaptic Transmission - drug effects Vasodilator Agents - pharmacology |
| title | Modulation of Synaptic Transmission by Nociceptin/Orphanin FQ and Nocistatin in the Spinal Cord Dorsal Horn of Mutant Mice Lacking the Nociceptin/Orphanin FQ Receptor |
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