2-Arachidonoylglycerol

changed changed 477212639 2-Ara-Gl.svg skin-invert-image 200px 2-arachidonoylglycerol 3D BS.png bg-transparent 200px 2-O-[(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoyl]glycerol 1,3-Dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate 2-AG, 2-arachidonoylglycerol 1/C23H38O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-23(26)27-22(20-24)21-25/h6-7,9-10,12-13,15-16,22,24-25H,2-5,8,11,14,17-21H2,1H3/b7-6-,10-9-,13-12-,16-15- RCRCTBLIHCHWDZ-DOFZRALJBN correct EBI 122972 correct chemspider 1S/C23H38O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-23(26)27-22(20-24)21-25/h6-7,9-10,12-13,15-16,22,24-25H,2-5,8,11,14,17-21H2,1H3/b7-6-,10-9-,13-12-,16-15- correct chemspider RCRCTBLIHCHWDZ-DOFZRALJSA-N correct CAS 53847-30-6 correct FDA 8D239QDW64 5282280 729 correct EBI 52392 O=C(OC(CO)CO)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC correct chemspider 4445451 23 38 4 378.3 g/mol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor.Stella N, Schweitzer P, Piomelli D A second endogenous cannabinoid that modulates long-term potentiation Nature 388 6644 773–8 August 1997 9285589 10.1038/42015 1997Natur.388..773S 4422311 https://cloudfront.escholarship.org/dist/prd/content/qt88z4q16s/qt88z4q16s.pdf free Sugiura T, Kodaka T, Nakane S Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds The Journal of Biological Chemistry 274 5 2794–801 January 1999 9915812 10.1074/jbc.274.5.2794 etal free It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present at relatively high levels in the central nervous system, with cannabinoid neuromodulatory effects. It has been found in bovine and human milk.Berrendero F. Sepe N. Ramos J. A. Di Marzo V. Fernández-Ruiz J. J. 1999-09-01 Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period Synapse (New York, N.Y.) 33 3 181–191 10.1002/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R 0887-4476 10420166 39220005 The chemical was first described in 1994–1995, although it had been discovered some time before that. The activities of phospholipase C (PLC) and diacylglycerol lipase (DAGL) mediate its formation.Witting Anke Walter Lisa Wacker Jennifer Möller Thomas Stella Nephi 2004-03-02 P2X7 receptors control 2-arachidonoylglycerol production by microglial cells Proceedings of the National Academy of Sciences of the United States of America 101 9 3214–3219 10.1073/pnas.0306707101 0027-8424 14976257 365769 2004PNAS..101.3214W free 2-AG is synthesized from arachidonic acid-containing diacylglycerol (DAG). Occurrence 2-AG, unlike anandamide (another endocannabinoid), is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in mouse and rat brain (~5–10 nmol/g tissue).Kondo S, Kondo H, Nakane S 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through Ca2+-dependent and -independent mechanisms FEBS Letters 429 2 152–6 June 1998 9650580 10.1016/S0014-5793(98)00581-X 10583431 etal 1998FEBSL.429..152K free Detection of 2-AG in brain tissue is complicated by the relative ease of its isomerization to 1-AG during standard lipid extraction conditions. It has been found in bovine as well as human milk.Fride E, Bregman T, Kirkham TC April 2005 Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood Experimental Biology and Medicine 230 4 225–234 10.1177/153537020523000401 15792943 25430588 http://www.ebmonline.org/cgi/reprint/230/4/225.pdf 2009-08-02 2007-10-23 https://web.archive.org/web/20090802181308/http://www.ebmonline.org/cgi/reprint/230/4/225.pdf dead The Endocannabinoid-CB Receptor System: Importance for development and in pediatric disease Neuroendocrinology Letters Nos.1/2, Feb-Apr Vol.25, 2004.Cannabinoids and Feeding: The Role of the Endogenous Cannabinoid System as a Trigger for Newborn Suckling https://web.archive.org/web/20201001042840/http://www.cannabis-med.org/data/pdf/2002-03-04-3.pdf 2020-10-01 Women and Cannabis: Medicine, Science, and Sociology, 2002 The Haworth Press, Inc. Discovery 2-AG was discovered by Raphael Mechoulam and his student Shimon Ben-Shabat.Pizzorno, Lara; MDiv; MA; LMT. "New Developments in Cannabinoid-Based Medicine: An Interview with Dr. Raphael Mechoulam" https://web.archive.org/web/20180619210540/http://www.lmreview.com/articles/print/new-developments-in-cannabinoid-based-medicine-an-interview-with-dr-raphael-mechoulam/ 2018-06-19 . Longevity Medicine Review. Retrieved 2011-05-26. 2-AG was a known chemical compound but its occurrence in mammals and its affinity for the cannabinoid receptors were first described in 1994–1995. A research group at Teikyo University reported the affinity of 2-AG for the cannabinoid receptors in 1994–1995,Sugiura T, Itoh K, Waku K, Hanahan DJ (1994) Proceedings of Japanese conference on the Biochemistry of Lipids, 36, 71-74 (in Japanese)Sugiura T, Kondo S, Sukagawa A 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain Biochem. Biophys. Res. Commun. 215 1 89–97 October 1995 7575630 10.1006/bbrc.1995.2437 etal 1995BBRC..215...89S but the isolation of 2-AG in the canine gut was first reported in 1995 by the research group of Raphael Mechoulam at the Hebrew University of Jerusalem, which additionally characterized its pharmacological properties in vivo.Mechoulam R, Ben-Shabat S, Hanuš L Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors Biochemical Pharmacology 50 1 83–90 June 1995 7605349 10.1016/0006-2952(95)00109-D etal 2-Arachidonoylglycerol, next with Anandamide, was the second endocannabinoid discovered. The cannabinoid established the existence of a cannabinoid neuromodulatory system in the nervous system.Marzo Vincenzo Di Cannabinoids (Neuroscience Intelligence Unit) 2004 Springer Georgetown, Texas 978-0-306-48228-1 99, 181 1st Pharmacology Unlike anandamide, formation of 2-AG is calcium-dependent and is mediated by the activities of phospholipase C (PLC) and diacylglycerol lipase (DAGL). 2-AG acts as a full agonist at the CB1 receptor.Savinainen JR, Järvinen T, Laine K, Laitinen JT Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes British Journal of Pharmacology 134 3 664–72 October 2001 11588122 1572991 10.1038/sj.bjp.0704297 At a concentration of 0.3 nM, 2-AG induces a rapid, transient increase in intracellular free calcium in NG108-15 neuroblastoma X glioma cells through a CB1 receptor-dependent mechanism. 2-AG is hydrolyzed in vitro by monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and the uncharacterized serine hydrolase enzymes ABHD2,Miller Melissa R. Mannowetz Nadja Iavarone Anthony T. Safavi Rojin Gracheva Elena O. Smith James F. Hill Rose Z. Bautista Diana M. Kirichok Yuriy Lishko Polina V. 2016-04-29 Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone Science en 352 6285 555–559 10.1126/science.aad6887 0036-8075 26989199 5373689 2016Sci...352..555M ABHD6 and ABHD12.Blankman JL, Simon GM, Cravatt BF A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol Chemistry & Biology 14 12 1347–56 December 2007 18096503 10.1016/j.chembiol.2007.11.006 2692834 The exact contribution of each of these enzymes to the termination of 2-AG signaling in vivo is unknown, though it is estimated that MAGL is responsible for ~85% of this activity in the brain. 21418147 2012 Savinainen JR Saario SM Laitinen JT The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors 204 2 267–76 10.1111/j.1748-1716.2011.02280.x 3320662 Acta Physiologica There have been identified transport proteins for 2-arachidonoylglycerol and anandamide. These include the heat shock proteins (Hsp70s) and fatty acid binding proteins (FABPs).Identification of intracellular carriers for the endocannabinoid anandamide 2009 Proceedings of the National Academy of Sciences of the United States of America 106 15 6375–6380 Kaczocha M. Glaser S.T. Deutsch D.G. 19307565 10.1073/pnas.0901515106 2669397 2009PNAS..106.6375K free Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins 2009 Chemistry & Biology 16 6 624–632 Oddi S. Fezza F. Pasquariello N. d'Agostino A. Catanzaro G. De Simone C. Rapino C. Finazzi-Agrò A. MacCarrone M. 19481477 10.1016/j.chembiol.2009.05.004 free Biosynthesis 2-Arachidonoylglycerol is synthesized from arachidonic acid-containing diacylglycerol (DAG), which is derived from the increase of inositol phospholipid metabolism by the action of diacylglycerol lipase. The molecule can also be formed from pathways like the hydrolysis derived (by diglyceride) from both phosphatidylcholine (PC) and phosphatidic acid (PAs) by the action of DAG lipase and the hydrolysis of arachidonic acid-containing lysophosphatidic acid by the action of a phosphatase.Murataeva N, Straiker A, Mackie K Mar 2014 Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS Br J Pharmacol 171 6 1379–91 10.1111/bph.12411 24102242 3954479 See also 2-Arachidonoyl glyceryl ether Endocannabinoid transporters References Notes 2 General references Dinh TP, Carpenter D, Leslie FM Brain monoglyceride lipase participating in endocannabinoid inactivation Proceedings of the National Academy of Sciences of the United States of America 99 16 10819–24 August 2002 12136125 125056 10.1073/pnas.152334899 2002PNAS...9910819D etal free Category:Endocannabinoids Category:Neurotransmitters Category:Fatty acid esters Category:CB1 receptor agonists Category:Glycine receptor antagonists Category:Glycerol esters Category:Arachidonyl compounds