Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and 2-Arachidonoylglycerol: Difference between pages

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477212639

| ImageFile = 2-Ara-Gl.svg

| ImageSize = 200px

| ImageFile2 = 2-arachidonoylglycerol 3D BS.png

| ImageSize2 = 200px

| IUPACName = 2-''O''-[(5''Z'',8''Z'',11''Z'',14''Z'')-Icosa-5,8,11,14-tetraenoyl]glycerol

| SystematicName = 1,3-Dihydroxypropan-2-yl (5''Z'',8''Z'',11''Z'',14''Z'')-icosa-5,8,11,14-tetraenoate

|Section1={{Chembox Identifiers

| InChI = 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-

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 53847-30-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 8D239QDW64

| PubChem = 5282280

| ChEBI_Ref = {{ebicite|correct|EBI}}

| MeSHName =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|Section2={{Chembox Properties

| Formula =

| C=23 | H=38 | O=4

| MolarMass = 378.3 g/mol

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

'''2-Arachidonoylglycerol''' ('''2-AG''') is an [[endocannabinoid]], an [[endogenous]] [[agonist]] of the [[CB1 receptor|CB₁ receptor]] and the primary endogenous ligand for the CB2 receptor.<ref name="pmid9285589">{{cite journal |vauthors=Stella N, Schweitzer P, Piomelli D |title=A second endogenous cannabinoid that modulates long-term potentiation |journal=Nature |volume=388 |issue=6644 |pages=773–8 |date=August 1997 |pmid=9285589 |doi=10.1038/42015 |bibcode=1997Natur.388..773S |s2cid=4422311 |url=https://cloudfront.escholarship.org/dist/prd/content/qt88z4q16s/qt88z4q16s.pdf|doi-access=free }}</ref><ref name="pmid9915812">{{cite journal |vauthors=Sugiura T, Kodaka T, Nakane S |title=Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds |journal=The Journal of Biological Chemistry |volume=274 |issue=5 |pages=2794–801 |date=January 1999 |pmid=9915812 |doi= 10.1074/jbc.274.5.2794|display-authors=etal|doi-access=free }}</ref> 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 maternal bovine and [[Breast milk|human milk]].<ref>{{Cite journal|last1=Berrendero|first1=F.|last2=Sepe|first2=N.|last3=Ramos|first3=J. A.|last4=Di Marzo|first4=V.|last5=Fernández-Ruiz|first5=J. J.|date=1999-09-01|title=Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period|url=https://pubmed.ncbi.nlm.nih.gov/10420166/|journal=Synapse (New York, N.Y.)|volume=33|issue=3|pages=181–191|doi=10.1002/(SICI)1098-2396(19990901)33:3<181::AID-SYN3>3.0.CO;2-R|issn=0887-4476|pmid=10420166|s2cid=39220005 }}</ref> 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.<ref>{{Cite journal|last1=Witting|first1=Anke|last2=Walter|first2=Lisa|last3=Wacker|first3=Jennifer|last4=Möller|first4=Thomas|last5=Stella|first5=Nephi|date=2004-03-02|title=P2X7 receptors control 2-arachidonoylglycerol production by microglial cells|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=101|issue=9|pages=3214–3219|doi=10.1073/pnas.0306707101|issn=0027-8424|pmid=14976257|pmc=365769|bibcode=2004PNAS..101.3214W|doi-access=free}}</ref> 2-AG is [[Biosynthesis|synthesized]] from [[arachidonic acid]]-containing [[Diglyceride|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&nbsp;nmol/g tissue).<ref name="pmid9915812"/><ref name="pmid9650580">{{cite journal |vauthors=Kondo S, Kondo H, Nakane S |title=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 |journal=FEBS Letters |volume=429 |issue=2 |pages=152–6 |date=June 1998 |pmid=9650580 |doi= 10.1016/S0014-5793(98)00581-X|s2cid=10583431 |display-authors=etal|doi-access=free }}</ref> 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 maternal bovine as well as human milk.<ref>{{cite journal |vauthors=Fride E, Bregman T, Kirkham TC |date=April 2005 | title = Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood |journal=Experimental Biology and Medicine | volume=230 |issue=4 |pages=225–234 |doi = 10.1177/153537020523000401 |pmid=15792943 |s2cid=25430588 |url=http://www.ebmonline.org/cgi/reprint/230/4/225.pdf }}</ref><ref>[http://www.nel.edu/pdf_/25_12/NEL251204A01_Fride_.pdf The Endocannabinoid-CB Receptor System: Importance for development and in pediatric disease] Neuroendocrinology Letters Nos.1/2, Feb-Apr Vol.25, 2004.</ref><ref>[http://www.cannabis-med.org/data/pdf/2002-03-04-3.pdf Cannabinoids and Feeding: The Role of the Endogenous Cannabinoid System as a Trigger for Newborn Suckling] {{Webarchive|url=https://web.archive.org/web/20201001042840/http://www.cannabis-med.org/data/pdf/2002-03-04-3.pdf |date=2020-10-01 }} Women and Cannabis: Medicine, Science, and Sociology, 2002 The Haworth Press, Inc.</ref>

==Discovery==

2-AG was discovered by [[Raphael Mechoulam]] and his student Shimon Ben-Shabat.<ref>Pizzorno, Lara; MDiv; MA; LMT. [http://www.lmreview.com/articles/print/new-developments-in-cannabinoid-based-medicine-an-interview-with-dr-raphael-mechoulam/ "New Developments in Cannabinoid-Based Medicine: An Interview with Dr. Raphael Mechoulam"] {{Webarchive|url=https://web.archive.org/web/20180619210540/http://www.lmreview.com/articles/print/new-developments-in-cannabinoid-based-medicine-an-interview-with-dr-raphael-mechoulam/ |date=2018-06-19 }}. Longevity Medicine Review. Retrieved 2011-05-26.</ref> 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,<ref>Sugiura T, Itoh K, Waku K, Hanahan DJ (1994) Proceedings of Japanese conference on the Biochemistry of Lipids, 36, 71-74 (in Japanese)</ref><ref name="pmid7575630">{{cite journal |vauthors=Sugiura T, Kondo S, Sukagawa A |title=2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain |journal=[[Biochem. Biophys. Res. Commun.]] |volume=215 |issue=1 |pages=89–97 |date=October 1995 |pmid=7575630 |doi= 10.1006/bbrc.1995.2437|display-authors=etal}}</ref> 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''.<ref name="pmid7605349">{{cite journal |vauthors=Mechoulam R, Ben-Shabat S, Hanuš L |title=Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors |journal=[[Biochemical Pharmacology (journal)|Biochemical Pharmacology]] |volume=50 |issue=1 |pages=83–90 |date=June 1995 |pmid=7605349 |doi= 10.1016/0006-2952(95)00109-D|display-authors=etal}}</ref> 2-Arachidonoylglycerol, next with [[Anandamide]], was the second [[endocannabinoid]] discovered. The cannabinoid established the existence of a cannabinoid neuromodulatory system in the [[nervous system]].<ref>{{cite book|last=Marzo|first=Vincenzo Di|title=Cannabinoids (Neuroscience Intelligence Unit)|year=2004|publisher=[[Springer Science+Business Media|Springer]]|location=[[Georgetown, Texas]]|isbn=978-0-306-48228-1|pages=99, 181|edition=1st}}</ref>

==Pharmacology==

Unlike [[anandamide]], formation of 2-AG is calcium-dependent and is mediated by the activities of [[phospholipase C]] (PLC) and [[diacylglycerol lipase]] (DAGL).<ref name="pmid9915812"/> 2-AG acts as a full agonist at the CB1 receptor.<ref name="pmid11588122">{{cite journal |vauthors=Savinainen JR, Järvinen T, Laine K, Laitinen JT |title=Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes |journal=[[British Journal of Pharmacology]] |volume=134 |issue=3 |pages=664–72 |date=October 2001 |pmid=11588122 |pmc=1572991 |doi=10.1038/sj.bjp.0704297 }}</ref> At a concentration of 0.3&nbsp;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.<ref name="pmid9915812"/> 2-AG is hydrolyzed ''in vitro'' by [[monoacylglycerol lipase]] (MAGL), [[fatty acid amide hydrolase]] (FAAH), and the uncharacterized [[serine hydrolase]] enzymes [[ABHD2]],<ref>{{Cite journal|last1=Miller|first1=Melissa R.|last2=Mannowetz|first2=Nadja|last3=Iavarone|first3=Anthony T.|last4=Safavi|first4=Rojin|last5=Gracheva|first5=Elena O.|last6=Smith|first6=James F.|last7=Hill|first7=Rose Z.|last8=Bautista|first8=Diana M.|last9=Kirichok|first9=Yuriy|last10=Lishko|first10=Polina V.|date=2016-04-29|title=Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone|url= |journal=Science|language=en|volume=352|issue=6285|pages=555–559|doi=10.1126/science.aad6887|issn=0036-8075|pmid=26989199|pmc=5373689|bibcode=2016Sci...352..555M}}</ref> [[ABHD6]] and [[ABHD12]].<ref name="pmid18096503">{{cite journal |vauthors=Blankman JL, Simon GM, Cravatt BF |title=A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol |journal=Chemistry & Biology |volume=14 |issue=12 |pages=1347–56 |date=December 2007 |pmid=18096503 |doi=10.1016/j.chembiol.2007.11.006 |pmc=2692834}}</ref> 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.<ref>{{cite journal | pmid = 21418147 | year = 2012 | last1 = Savinainen | first1 = JR | last2 = Saario | first2 = SM | last3 = Laitinen | first3 = JT | title = The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors | volume = 204 | issue = 2 | pages = 267–76 | doi = 10.1111/j.1748-1716.2011.02280.x | pmc = 3320662 | journal = Acta Physiologica }}</ref> There have been identified [[Endocannabinoid transporters|transport proteins]] for 2-arachidonoylglycerol and anandamide. These include the [[heat shock protein]]s ([[Hsp70]]s) and [[Fatty acid-binding protein|fatty acid binding proteins]] (FABPs).<ref name = "pnasus2009">{{cite journal |title=Identification of intracellular carriers for the endocannabinoid anandamide |year=2009 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=106 | issue=15 |pages=6375–6380 |last1=Kaczocha |first1=M. |last2=Glaser |first2=S.T. |last3=Deutsch |first3=D.G. |pmid=19307565 |doi=10.1073/pnas.0901515106 |pmc=2669397|bibcode=2009PNAS..106.6375K |doi-access=free }}</ref><ref name = "cb2009">{{cite journal |title=Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins |year=2009 | journal=Chemistry & Biology |volume=16 |issue=6 |pages=624–632 |last1=Oddi | first1=S. |last2=Fezza |first2=F. |last3=Pasquariello |first3=N. | last4=d'Agostino |first4=A. |last5=Catanzaro |first5=G. |last6=De Simone | first6=C. |last7=Rapino |first7=C. |last8=Finazzi-Agrò |first8=A. | last9=MacCarrone |first9=M. |pmid=19481477 | doi=10.1016/j.chembiol.2009.05.004|doi-access=free }}</ref>

==Biosynthesis==

2-Arachidonoylglycerol is [[Biosynthesis|synthesized]] from [[arachidonic acid]]-containing [[Diglyceride|diacylglycerol (DAG)]], which is derived from the increase of [[Lipid signaling|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]].<ref>{{cite journal |vauthors=Murataeva N, Straiker A, Mackie K | date = Mar 2014 | title = Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS | journal = Br J Pharmacol | volume = 171 | issue = 6| pages = 1379–91 | doi = 10.1111/bph.12411 | pmid = 24102242 | pmc = 3954479 }}</ref>

==See also==

* [[2-Arachidonoyl glyceryl ether]]

* [[Endocannabinoid transporters]]

==References==

===Notes===

{{Reflist|2}}

===General references===

*{{cite journal |vauthors=Dinh TP, Carpenter D, Leslie FM |title=Brain monoglyceride lipase participating in endocannabinoid inactivation |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=99 |issue=16 |pages=10819–24 |date=August 2002 |pmid=12136125 |pmc=125056 |doi=10.1073/pnas.152334899 |bibcode=2002PNAS...9910819D |display-authors=etal|doi-access=free }}

{{Cannabinoids}}

{{Neurotransmitters}}

{{Cannabinoidergics}}

{{Glycinergics}}

{{DEFAULTSORT:Arachidonoylglycerol, 2-}}

[[Category:Endocannabinoids]]

[[Category:Neurotransmitters]]

[[Category:Fatty acid esters]]

[[Category:CB1 receptor agonists]]

[[Category:Glycine receptor antagonists]]

[[Category:Glycerol esters]]

[[Category:Arachidonyl compounds]]