Formation and inactivation of endogenous cannabinoid anandamide in central neurons
ANANDAMIDE ( N -arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors 1–4 , yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that a...
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| Veröffentlicht in: | Nature (London) 1994-12, Vol.372 (6507), p.686-691 |
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| creator | Di Marzo, Vincenzo Fontana, Angelo Cadas, Hugues Schinelli, Sergio Cimino, Guido Schwartz, Jean-Charles Piomelli, Danlele |
| description | ANANDAMIDE (
N
-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors
1–4
, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phos-phodiesterase-mediated cleavage of a novel phospholipid precursor,
N
-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others
5,6
indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger. |
| doi_str_mv | 10.1038/372686a0 |
| format | Article |
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N
-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors
1–4
, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phos-phodiesterase-mediated cleavage of a novel phospholipid precursor,
N
-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others
5,6
indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/372686a0</identifier><identifier>PMID: 7990962</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Arachidonic Acids - metabolism ; Astrocytes - metabolism ; Biochemistry ; Biochemistry and metabolism ; Biological and medical sciences ; Brain ; Calcium ; Cannabinoids - metabolism ; Cells, Cultured ; Central nervous system ; Central Nervous System - drug effects ; Central Nervous System - metabolism ; Cerebral Cortex - metabolism ; Corpus Striatum - metabolism ; Endocannabinoids ; Fundamental and applied biological sciences. Psychology ; Humanities and Social Sciences ; Inactivation ; Ionomycin - pharmacology ; letter ; Marijuana ; multidisciplinary ; Neurology ; Neurons - drug effects ; Neurons - metabolism ; Phosphatidylethanolamines - metabolism ; Polyunsaturated Alkamides ; Rats ; Science ; Science (multidisciplinary) ; Signal Transduction ; Vertebrates: nervous system and sense organs</subject><ispartof>Nature (London), 1994-12, Vol.372 (6507), p.686-691</ispartof><rights>Springer Nature Limited 1994</rights><rights>1995 INIST-CNRS</rights><rights>Copyright Macmillan Journals Ltd. Dec 15, 1994</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-34da55d7d3887585c9692a2361071640e937467b305372439f5930e9774ac5cb3</citedby><cites>FETCH-LOGICAL-c497t-34da55d7d3887585c9692a2361071640e937467b305372439f5930e9774ac5cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/372686a0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/372686a0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3398993$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7990962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di Marzo, Vincenzo</creatorcontrib><creatorcontrib>Fontana, Angelo</creatorcontrib><creatorcontrib>Cadas, Hugues</creatorcontrib><creatorcontrib>Schinelli, Sergio</creatorcontrib><creatorcontrib>Cimino, Guido</creatorcontrib><creatorcontrib>Schwartz, Jean-Charles</creatorcontrib><creatorcontrib>Piomelli, Danlele</creatorcontrib><title>Formation and inactivation of endogenous cannabinoid anandamide in central neurons</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>ANANDAMIDE (
N
-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors
1–4
, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phos-phodiesterase-mediated cleavage of a novel phospholipid precursor,
N
-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others
5,6
indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.</description><subject>Animals</subject><subject>Arachidonic Acids - metabolism</subject><subject>Astrocytes - metabolism</subject><subject>Biochemistry</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Calcium</subject><subject>Cannabinoids - metabolism</subject><subject>Cells, Cultured</subject><subject>Central nervous system</subject><subject>Central Nervous System - drug effects</subject><subject>Central Nervous System - metabolism</subject><subject>Cerebral Cortex - metabolism</subject><subject>Corpus Striatum - metabolism</subject><subject>Endocannabinoids</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humanities and Social Sciences</subject><subject>Inactivation</subject><subject>Ionomycin - pharmacology</subject><subject>letter</subject><subject>Marijuana</subject><subject>multidisciplinary</subject><subject>Neurology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Phosphatidylethanolamines - metabolism</subject><subject>Polyunsaturated Alkamides</subject><subject>Rats</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkV9LHTEQxYNU7NUKfgFhKaL2YXU2__MoolYQCqV9XuZmsxLZTTTZFfz2Ru5VwYJ9Csz5zcmZGUL2GjhpgOlTpqjUEmGDLBquZM2lVl_IAoDqGjSTX8l2zncAIBrFt8iWMgaMpAvy-zKmEScfQ4Whq3xAO_nHVSH2lQtdvHUhzrmyGAIufYi-K2iBcfSdKx2VdWFKOFTBzSmG_I1s9jhkt7t-d8jfy4s_5z_rm19X1-dnN7XlRk014x0K0amOaa2EFtZIQ5Ey2YBqJAdnmOJSLRmIMh1npheGlapSHK2wS7ZDDle-9yk-zC5P7eizdcOAwZXArSo7KJ2igEefg5xRkGUx_7VspARKJSvg9w_gXZxTKOO2FDjnRoMq0PEKsinmnFzf3ic_YnpqG2hfzta-nq2g-2u_eTm67g1c36noB2sds8WhTxisz28YY0Yb8xLrxwrLRQm3Lr3H-ufLZ7qhqSs</recordid><startdate>19941215</startdate><enddate>19941215</enddate><creator>Di Marzo, Vincenzo</creator><creator>Fontana, Angelo</creator><creator>Cadas, Hugues</creator><creator>Schinelli, Sergio</creator><creator>Cimino, Guido</creator><creator>Schwartz, Jean-Charles</creator><creator>Piomelli, Danlele</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7U7</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>19941215</creationdate><title>Formation and inactivation of endogenous cannabinoid anandamide in central neurons</title><author>Di Marzo, Vincenzo ; Fontana, Angelo ; Cadas, Hugues ; Schinelli, Sergio ; Cimino, Guido ; Schwartz, Jean-Charles ; Piomelli, Danlele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-34da55d7d3887585c9692a2361071640e937467b305372439f5930e9774ac5cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Arachidonic Acids - metabolism</topic><topic>Astrocytes - metabolism</topic><topic>Biochemistry</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>Calcium</topic><topic>Cannabinoids - metabolism</topic><topic>Cells, Cultured</topic><topic>Central nervous system</topic><topic>Central Nervous System - drug effects</topic><topic>Central Nervous System - metabolism</topic><topic>Cerebral Cortex - metabolism</topic><topic>Corpus Striatum - metabolism</topic><topic>Endocannabinoids</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humanities and Social Sciences</topic><topic>Inactivation</topic><topic>Ionomycin - pharmacology</topic><topic>letter</topic><topic>Marijuana</topic><topic>multidisciplinary</topic><topic>Neurology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Phosphatidylethanolamines - metabolism</topic><topic>Polyunsaturated Alkamides</topic><topic>Rats</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di Marzo, Vincenzo</creatorcontrib><creatorcontrib>Fontana, Angelo</creatorcontrib><creatorcontrib>Cadas, Hugues</creatorcontrib><creatorcontrib>Schinelli, Sergio</creatorcontrib><creatorcontrib>Cimino, Guido</creatorcontrib><creatorcontrib>Schwartz, Jean-Charles</creatorcontrib><creatorcontrib>Piomelli, Danlele</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>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical 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>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di Marzo, Vincenzo</au><au>Fontana, Angelo</au><au>Cadas, Hugues</au><au>Schinelli, Sergio</au><au>Cimino, Guido</au><au>Schwartz, Jean-Charles</au><au>Piomelli, Danlele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Formation and inactivation of endogenous cannabinoid anandamide in central neurons</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1994-12-15</date><risdate>1994</risdate><volume>372</volume><issue>6507</issue><spage>686</spage><epage>691</epage><pages>686-691</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>ANANDAMIDE (
N
-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors
1–4
, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phos-phodiesterase-mediated cleavage of a novel phospholipid precursor,
N
-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others
5,6
indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>7990962</pmid><doi>10.1038/372686a0</doi><tpages>6</tpages></addata></record> |
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| ispartof | Nature (London), 1994-12, Vol.372 (6507), p.686-691 |
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| subjects | Animals Arachidonic Acids - metabolism Astrocytes - metabolism Biochemistry Biochemistry and metabolism Biological and medical sciences Brain Calcium Cannabinoids - metabolism Cells, Cultured Central nervous system Central Nervous System - drug effects Central Nervous System - metabolism Cerebral Cortex - metabolism Corpus Striatum - metabolism Endocannabinoids Fundamental and applied biological sciences. Psychology Humanities and Social Sciences Inactivation Ionomycin - pharmacology letter Marijuana multidisciplinary Neurology Neurons - drug effects Neurons - metabolism Phosphatidylethanolamines - metabolism Polyunsaturated Alkamides Rats Science Science (multidisciplinary) Signal Transduction Vertebrates: nervous system and sense organs |
| title | Formation and inactivation of endogenous cannabinoid anandamide in central neurons |
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