2-arachidonylglycerol

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{{Drugbox
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| IUPAC_name        = 1,3-dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
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| CAS_number        = 53847-30-6
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| CAS_supplemental  =
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| ATC_suffix = BA03
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| ATC_supplemental  =
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| PubChem          = 123917
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| ChemSpiderID      =
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| chemical_formula  =C<sub>2</sub><sub>3</sub>H<sub>3</sub><sub>8</sub>O<sub>4</sub>
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| molecular_weight  = 378.55
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| smiles            = CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO
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| synonyms          = 2-AG
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| density          =
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| melting_point    =
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| boiling_point    =
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| solubility        =
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| specific_rotation =
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| sec_combustion    =
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| bioavailability  =
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| protein_bound    =
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| metabolism        =
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| elimination_half-life =
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| excretion        =
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| pregnancy_category=
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| dependency_liability =
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| routes_of_administration =
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}}
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[http://172.141.127.22/raghava/hmrbase/test_extract.php?db=arun&table=nphormonet&id=1002&show=SHOW-3D Show 3-D Structure]
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==Description==
==Description==
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binds to cannabinoid receptors; structure in first source
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'''2-Arachidonoylglycerol''' (2-AG), is an [[endocannabinoid]], an endogenous [[agonist]] of the [[CB1 receptor]].<ref name="pmid9285589">{{cite journal |author=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 |year=1997 |month=August |pmid=9285589 |doi=10.1038/42015 |url=}}</ref><ref name="pmid9915812">{{cite journal |author=Sugiura T, Kodaka T, Nakane S, ''et al'' |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 |year=1999 |month=January |pmid=9915812 |doi= |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9915812}}</ref>
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<jmol>
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It is an [[ester]] formed from the [[omega-6 fatty acid]] [[arachidonic acid]] and [[glycerol]]. 
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  <jmolApplet>
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==Discovery==
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    <urlContents>hmrbase/NPH210.SDF</urlContents>
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2-AG was a known chemical compound but its occurence in mammalians 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 |author=Sugiura T, Kondo S, Sukagawa A, ''et al'' |title=2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain |journal=[[Biochem. Biophys. Res. Commun.]] |volume=215 |issue=1 |pages=89–97 |year=1995 |month=October |pmid=7575630 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0006291X85724370 |accessdate=2009-01-27}}</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 |author=Mechoulam R, Ben-Shabat S, Hanus L, ''et al'' |title=Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors |journal=Biochemical pharmacology |volume=50 |issue=1 |pages=83–90 |year=1995 |month=June |pmid=7605349 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/000629529500109D}}</ref>
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  </jmolApplet>
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</jmol>
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==General Properties==
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<b>*Molecular Weight</b>
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378.55
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<b>*Molecular Formula</b>
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C<sub>2</sub><sub>3</sub>H<sub>3</sub><sub>8</sub>O<sub>4</sub>
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<b>*IUPAC NAME</b>
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1,3-dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
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<b>*Canonical Smiles</b>
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CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO
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<b>*Isomeric Smiles</b>
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CCCCCC=C/CC=C/CC=C/CC=C/CCCC(=O)OC(CO)CO
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==PhysioChemical Properties==
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<b>*Melting Point</b>
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<b>*LogP</b>
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==Occurence==
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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).<ref name="pmid9915812"/><ref name="pmid9650580">{{cite journal |author=Kondo S, Kondo H, Nakane S, ''et al'' |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 |year=1998 |month=June |pmid=9650580 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0014-5793(98)00581-X}}</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.
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It has been found in maternal bovine and human milk.<ref>{{cite journal | author = Fride E, Bregman T, Kirkham TC.  | year = 2005  | month = April  | 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 = 10.1371/journal.pbio.0020286  |pmid=15792943 |url=http://www.ebmonline.org/cgi/reprint/230/4/225.pdf | format = | accessdate = }}</ref>
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==Pharmacology==
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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 |author=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 |year=2001 |month=October |pmid=11588122 |pmc=1572991 |doi=10.1038/sj.bjp.0704297 |url=}}</ref> 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.<ref name="pmid9915812"/> 2-AG is hydrolyzed ''in vitro'' by [[monoacylglycerol lipase]] (MAGL), [[fatty acid amide hydrolase]] (FAAH), and the uncharacterized serine hydrolase enzymes ABHD6 and ABHD12.<ref name="pmid18096503">{{cite journal |author=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 |year=2007 |month=December |pmid=18096503 |doi=10.1016/j.chembiol.2007.11.006 |url=}}</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.
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<b>*Water Solubility</b>
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== References ==
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===Footnotes===
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<references/>
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===General references===
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{{cite journal |author=Dinh TP, Carpenter D, Leslie FM, ''et al'' |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 |year=2002 |month=August |pmid=12136125 |pmc=125056 |doi=10.1073/pnas.152334899 |url=}}
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{{Cannabinoids}}
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{{DEFAULTSORT:Arachidonoylglycerol, 2-}}
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[[Categories:Hormones]]
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[[Category:Hormones]]
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[[Category:HMRbase]]
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[[Category:Cannabinoids]]
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[[Category:Neurotransmitters]]
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[[Category:Carboxylate esters]]

Current revision


2-arachidonylglycerol
Systematic (IUPAC) name
1,3-dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
Identifiers
CAS number 53847-30-6
ATC code  ?
PubChem 123917
Chemical data
Formula C23H38O4
Mol. mass 378.55
SMILES eMolecules & PubChem
Synonyms 2-AG
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?

Legal status
Routes  ?

Show 3-D Structure

Contents

[edit] Description

2-Arachidonoylglycerol (2-AG), is an endocannabinoid, an endogenous agonist of the CB1 receptor.<ref name="pmid9285589">Stella N, Schweitzer P, Piomelli D (August 1997). "A second endogenous cannabinoid that modulates long-term potentiation". Nature 388 (6644): 773–8. doi:10.1038/42015. PMID 9285589. </ref><ref name="pmid9915812">Sugiura T, Kodaka T, Nakane S, et al (January 1999). "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. PMID 9915812. </ref> It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol.

[edit] Discovery

2-AG was a known chemical compound but its occurence in mammalians 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">Sugiura T, Kondo S, Sukagawa A, et al (October 1995). "2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain". Biochem. Biophys. Res. Commun. 215 (1): 89–97. PMID 7575630. Retrieved on 2009-01-27.</cite> </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 style="font-style:normal">Mechoulam R, Ben-Shabat S, Hanus L, et al (June 1995). "Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors". Biochemical pharmacology 50 (1): 83–90. PMID 7605349.</cite> </ref>

[edit] Occurence

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).<ref name="pmid9915812"/><ref name="pmid9650580"><cite style="font-style:normal">Kondo S, Kondo H, Nakane S, et al (June 1998). "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. PMID 9650580.</cite> </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 and human milk.<ref><cite style="font-style:normal">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. doi:10.1371/journal.pbio.0020286. PMID 15792943.</cite> </ref>

[edit] 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 style="font-style:normal">Savinainen JR, Järvinen T, Laine K, Laitinen JT (October 2001). "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. doi:10.1038/sj.bjp.0704297. PMID 11588122.</cite> </ref> 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.<ref name="pmid9915812"/> 2-AG is hydrolyzed in vitro by monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and the uncharacterized serine hydrolase enzymes ABHD6 and ABHD12.<ref name="pmid18096503"><cite style="font-style:normal">Blankman JL, Simon GM, Cravatt BF (December 2007). "A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol". Chemistry & biology 14 (12): 1347–56. doi:10.1016/j.chembiol.2007.11.006. PMID 18096503.</cite> </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.

[edit] References

[edit] Footnotes

<references/>

[edit] General references

<cite style="font-style:normal">Dinh TP, Carpenter D, Leslie FM, et al (August 2002). "Brain monoglyceride lipase participating in endocannabinoid inactivation". Proceedings of the National Academy of Sciences of the United States of America 99 (16): 10819–24. doi:10.1073/pnas.152334899. PMID 12136125.</cite>  Template:Cannabinoids



[edit] External Links

  • [1]Pubchem
  • [2]]KEGG Compound
  • [3]Human Metabolome DataBase

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