Direct Activation of Capsaicin Receptors by Products of Lipoxygenases: Endogenous Capsaicin-Like Substances
Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous a...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2000-05, Vol.97 (11), p.6155-6160 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Hwang, Sun Wook Cho, Hawon Kwak, Jiyeon Lee, Soon-Youl Kang, Chang-Joong Jung, Jooyoung Cho, Soohyun Min, Kyung Hoon Suh, Young-Ger Kim, Donghee Oh, Uhtaek |
| description | Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B4possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction. |
| doi_str_mv | 10.1073/pnas.97.11.6155 |
| format | Article |
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A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B4possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.97.11.6155</identifier><identifier>PMID: 10823958</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Analgesics ; Animals ; Biological Sciences ; capsaicin ; Capsaicin - analogs & derivatives ; Capsaicin - chemistry ; Capsaicin - pharmacology ; capsaicin receptors ; Capsicum ; Cell Line ; Cells, Cultured ; Dinoprostone - chemistry ; Dinoprostone - pharmacology ; Eicosanoids ; Eicosanoids - chemistry ; Eicosanoids - pharmacology ; Enzymes ; Ganglia, Spinal - cytology ; Humans ; hydroxyeicosatetraenoic acids ; Hydroxyeicosatetraenoic Acids - chemistry ; Hydroxyeicosatetraenoic Acids - pharmacology ; Inflammation ; Ion Channel Gating - drug effects ; leukotriene B4 ; Leukotriene B4 - pharmacology ; Leukotrienes - chemistry ; Leukotrienes - pharmacology ; Ligands ; Lipid Peroxides - chemistry ; Lipid Peroxides - pharmacology ; Lipids ; Lipoxygenase - metabolism ; Molecular Structure ; Neurology ; Neurons ; Neurons, Afferent - drug effects ; Neuroscience ; Pain ; Prostaglandin D2 - chemistry ; Prostaglandin D2 - pharmacology ; Prostaglandin H2 ; Prostaglandins H - chemistry ; Prostaglandins H - pharmacology ; Rats ; Receptors ; Receptors, Drug - drug effects ; Receptors, Drug - physiology ; Sensory neurons ; Spinal ganglia ; Structure-Activity Relationship ; TRPV cation channels</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2000-05, Vol.97 (11), p.6155-6160</ispartof><rights>Copyright 1993-2000 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences May 23, 2000</rights><rights>Copyright © 2000, The National Academy of Sciences 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c611t-a890641776f3888ee40672a96be03311cce50d2a37774a0f2a03ce7344d485a23</citedby><cites>FETCH-LOGICAL-c611t-a890641776f3888ee40672a96be03311cce50d2a37774a0f2a03ce7344d485a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/97/11.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/122597$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/122597$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10823958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hwang, Sun Wook</creatorcontrib><creatorcontrib>Cho, Hawon</creatorcontrib><creatorcontrib>Kwak, Jiyeon</creatorcontrib><creatorcontrib>Lee, Soon-Youl</creatorcontrib><creatorcontrib>Kang, Chang-Joong</creatorcontrib><creatorcontrib>Jung, Jooyoung</creatorcontrib><creatorcontrib>Cho, Soohyun</creatorcontrib><creatorcontrib>Min, Kyung Hoon</creatorcontrib><creatorcontrib>Suh, Young-Ger</creatorcontrib><creatorcontrib>Kim, Donghee</creatorcontrib><creatorcontrib>Oh, Uhtaek</creatorcontrib><title>Direct Activation of Capsaicin Receptors by Products of Lipoxygenases: Endogenous Capsaicin-Like Substances</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B4possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>capsaicin</subject><subject>Capsaicin - analogs & derivatives</subject><subject>Capsaicin - chemistry</subject><subject>Capsaicin - pharmacology</subject><subject>capsaicin receptors</subject><subject>Capsicum</subject><subject>Cell Line</subject><subject>Cells, Cultured</subject><subject>Dinoprostone - chemistry</subject><subject>Dinoprostone - pharmacology</subject><subject>Eicosanoids</subject><subject>Eicosanoids - chemistry</subject><subject>Eicosanoids - pharmacology</subject><subject>Enzymes</subject><subject>Ganglia, Spinal - cytology</subject><subject>Humans</subject><subject>hydroxyeicosatetraenoic acids</subject><subject>Hydroxyeicosatetraenoic Acids - chemistry</subject><subject>Hydroxyeicosatetraenoic Acids - pharmacology</subject><subject>Inflammation</subject><subject>Ion Channel Gating - drug effects</subject><subject>leukotriene B4</subject><subject>Leukotriene B4 - pharmacology</subject><subject>Leukotrienes - chemistry</subject><subject>Leukotrienes - pharmacology</subject><subject>Ligands</subject><subject>Lipid Peroxides - chemistry</subject><subject>Lipid Peroxides - pharmacology</subject><subject>Lipids</subject><subject>Lipoxygenase - metabolism</subject><subject>Molecular Structure</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons, Afferent - drug effects</subject><subject>Neuroscience</subject><subject>Pain</subject><subject>Prostaglandin D2 - chemistry</subject><subject>Prostaglandin D2 - pharmacology</subject><subject>Prostaglandin H2</subject><subject>Prostaglandins H - chemistry</subject><subject>Prostaglandins H - pharmacology</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Drug - drug effects</subject><subject>Receptors, Drug - physiology</subject><subject>Sensory neurons</subject><subject>Spinal ganglia</subject><subject>Structure-Activity Relationship</subject><subject>TRPV cation channels</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkt1vFCEUxYnR2G312QcTM_FBn2bLBWaAxpdmWz-STTR-PBOWYSrb2WEEpun-9zLZ1V2NiU9A7u8c7uWA0DPAc8Ccng-9jnPJ5wDzGqrqAZoBllDWTOKHaIYx4aVghJ2g0xjXGGNZCfwYnQAWhOb9DN1euWBNKi5Ncnc6Od8Xvi0WeojaGdcXn62xQ_IhFqtt8Sn4ZjQpTsjSDf5-e2NzAzZeFNd94_PBj_EgLpfu1hZfxlVMujc2PkGPWt1F-3S_nqFvb6-_Lt6Xy4_vPiwul6WpAVKphcQ1A87rlgohrGW45kTLemUxpQDG2Ao3RFPOOdO4JRpTYzllrGGi0oSeoTc732FcbWxjbJ-C7tQQ3EaHrfLaqT8rvfuubvydAlFxluWv9vLgf4w2JrVx0diu073N8ykOQDHl8F8QeEUElxP48i9w7cfQ5zdQBAOlglOZofMdZIKPMdj2d8OA1RS2msJWkisANYWdFS-O5zzid-lm4PUemJS_ygcH1Y5dl-x9OrL6N5mB5ztgHfNvOFxFSCU5_QlNYse7</recordid><startdate>20000523</startdate><enddate>20000523</enddate><creator>Hwang, Sun Wook</creator><creator>Cho, Hawon</creator><creator>Kwak, Jiyeon</creator><creator>Lee, Soon-Youl</creator><creator>Kang, Chang-Joong</creator><creator>Jung, Jooyoung</creator><creator>Cho, Soohyun</creator><creator>Min, Kyung Hoon</creator><creator>Suh, Young-Ger</creator><creator>Kim, Donghee</creator><creator>Oh, Uhtaek</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</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>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>20000523</creationdate><title>Direct Activation of Capsaicin Receptors by Products of Lipoxygenases: Endogenous Capsaicin-Like Substances</title><author>Hwang, Sun Wook ; Cho, Hawon ; Kwak, Jiyeon ; Lee, Soon-Youl ; Kang, Chang-Joong ; Jung, Jooyoung ; Cho, Soohyun ; Min, Kyung Hoon ; Suh, Young-Ger ; Kim, Donghee ; Oh, Uhtaek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c611t-a890641776f3888ee40672a96be03311cce50d2a37774a0f2a03ce7344d485a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>capsaicin</topic><topic>Capsaicin - analogs & derivatives</topic><topic>Capsaicin - chemistry</topic><topic>Capsaicin - pharmacology</topic><topic>capsaicin receptors</topic><topic>Capsicum</topic><topic>Cell Line</topic><topic>Cells, Cultured</topic><topic>Dinoprostone - chemistry</topic><topic>Dinoprostone - pharmacology</topic><topic>Eicosanoids</topic><topic>Eicosanoids - chemistry</topic><topic>Eicosanoids - pharmacology</topic><topic>Enzymes</topic><topic>Ganglia, Spinal - cytology</topic><topic>Humans</topic><topic>hydroxyeicosatetraenoic acids</topic><topic>Hydroxyeicosatetraenoic Acids - chemistry</topic><topic>Hydroxyeicosatetraenoic Acids - pharmacology</topic><topic>Inflammation</topic><topic>Ion Channel Gating - drug effects</topic><topic>leukotriene B4</topic><topic>Leukotriene B4 - pharmacology</topic><topic>Leukotrienes - chemistry</topic><topic>Leukotrienes - pharmacology</topic><topic>Ligands</topic><topic>Lipid Peroxides - chemistry</topic><topic>Lipid Peroxides - pharmacology</topic><topic>Lipids</topic><topic>Lipoxygenase - metabolism</topic><topic>Molecular Structure</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons, Afferent - drug effects</topic><topic>Neuroscience</topic><topic>Pain</topic><topic>Prostaglandin D2 - chemistry</topic><topic>Prostaglandin D2 - pharmacology</topic><topic>Prostaglandin H2</topic><topic>Prostaglandins H - chemistry</topic><topic>Prostaglandins H - pharmacology</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Drug - drug effects</topic><topic>Receptors, Drug - physiology</topic><topic>Sensory neurons</topic><topic>Spinal ganglia</topic><topic>Structure-Activity Relationship</topic><topic>TRPV cation channels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwang, Sun Wook</creatorcontrib><creatorcontrib>Cho, Hawon</creatorcontrib><creatorcontrib>Kwak, Jiyeon</creatorcontrib><creatorcontrib>Lee, Soon-Youl</creatorcontrib><creatorcontrib>Kang, Chang-Joong</creatorcontrib><creatorcontrib>Jung, Jooyoung</creatorcontrib><creatorcontrib>Cho, Soohyun</creatorcontrib><creatorcontrib>Min, Kyung Hoon</creatorcontrib><creatorcontrib>Suh, Young-Ger</creatorcontrib><creatorcontrib>Kim, Donghee</creatorcontrib><creatorcontrib>Oh, Uhtaek</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Hwang, Sun Wook</au><au>Cho, Hawon</au><au>Kwak, Jiyeon</au><au>Lee, Soon-Youl</au><au>Kang, Chang-Joong</au><au>Jung, Jooyoung</au><au>Cho, Soohyun</au><au>Min, Kyung Hoon</au><au>Suh, Young-Ger</au><au>Kim, Donghee</au><au>Oh, Uhtaek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct Activation of Capsaicin Receptors by Products of Lipoxygenases: Endogenous Capsaicin-Like Substances</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2000-05-23</date><risdate>2000</risdate><volume>97</volume><issue>11</issue><spage>6155</spage><epage>6160</epage><pages>6155-6160</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B4possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>10823958</pmid><doi>10.1073/pnas.97.11.6155</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2000-05, Vol.97 (11), p.6155-6160 |
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| subjects | Analgesics Animals Biological Sciences capsaicin Capsaicin - analogs & derivatives Capsaicin - chemistry Capsaicin - pharmacology capsaicin receptors Capsicum Cell Line Cells, Cultured Dinoprostone - chemistry Dinoprostone - pharmacology Eicosanoids Eicosanoids - chemistry Eicosanoids - pharmacology Enzymes Ganglia, Spinal - cytology Humans hydroxyeicosatetraenoic acids Hydroxyeicosatetraenoic Acids - chemistry Hydroxyeicosatetraenoic Acids - pharmacology Inflammation Ion Channel Gating - drug effects leukotriene B4 Leukotriene B4 - pharmacology Leukotrienes - chemistry Leukotrienes - pharmacology Ligands Lipid Peroxides - chemistry Lipid Peroxides - pharmacology Lipids Lipoxygenase - metabolism Molecular Structure Neurology Neurons Neurons, Afferent - drug effects Neuroscience Pain Prostaglandin D2 - chemistry Prostaglandin D2 - pharmacology Prostaglandin H2 Prostaglandins H - chemistry Prostaglandins H - pharmacology Rats Receptors Receptors, Drug - drug effects Receptors, Drug - physiology Sensory neurons Spinal ganglia Structure-Activity Relationship TRPV cation channels |
| title | Direct Activation of Capsaicin Receptors by Products of Lipoxygenases: Endogenous Capsaicin-Like Substances |
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