2-Arachidonoylglycerol: Difference between revisions

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{{Chembox new
{{chembox
| ImageFile = 2ag.svg
| ImageSize = 250px
| ImageSize = 250px
| IUPACName = ((5Z,8Z,11Z,14Z)-1,3-dihydroxypropan-2-yl icosa-5,8,11,14-tetraenoate
| IUPACName = 1,3-Dihydroxy-2-propanyl (5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraenoate
| OtherNames = 2-AG, 2-arachidonoylglycerol
| OtherNames = 2-AG, 2-arachidonoylglycerol
| Section1 = {{Chembox Identifiers
| Section1 = {{Chembox Identifiers
|  CASNo = 53847-30-6
|  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-
|  PubChem =  
| InChIKey = RCRCTBLIHCHWDZ-DOFZRALJBN
|  SMILES =  
| CASNo = 53847-30-6
|  MeSHName =  
|  PubChem = 5282280
| IUPHAR_ligand = 729
|  SMILES = O=C(OC(CO)CO)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
|  MeSHName =
|  ChemSpiderID = 4445451
   }}
   }}
| Section2 = {{Chembox Properties
| Section2 = {{Chembox Properties
|  Formula = C<sub>23</sub>H<sub>38</sub>O<sub>4</sub>
|  Formula = C<sub>23</sub>H<sub>38</sub>O<sub>4</sub>
|  MolarMass = 378.6 g/mol
|  MolarMass = 378.3 g/mol
|  Appearance =  
|  Appearance =
|  Density =  
|  Density =
|  MeltingPt =  
|  MeltingPt =
|  BoilingPt =  
|  BoilingPt =
   }}
   }}
| Section3 = {{Chembox Hazards
| Section3 = {{Chembox Hazards
|  Solubility =  
|  Solubility =
|  MainHazards =  
|  MainHazards =
|  FlashPt =  
|  FlashPt =
|  Autoignition =  
|  Autoignition =
   }}
   }}
}}
}}
{{EH}}


==Overview==
'''2-Arachidonoylglycerol''' ('''2-AG''') is an [[endocannabinoid]], an [[endogenous]] [[agonist]] of the [[CB1 receptor|CB<sub>1</sub> 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= 10.1074/jbc.274.5.2794|url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9915812}}</ref> It is an [[ester]] formed from the [[omega-6 fatty acid]] [[arachidonic acid]] and [[glycerol]].
'''2-Arachidonoylglycerol''' (2-AG) is an [[endocannabinoid]], an endogenous [[agonist]] of the [[CB1 receptor]].<ref name="Ste">Stella, N., Schweitzer, P., Piomelli, D. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388 773-778 (1997).</ref><ref name="Sug">Sugiura, T., Kodaka, T., Nakane, S., et al. Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J Biol Chem 274 2794-2801 (1999).</ref> It is an [[ester]] formed from the [[omega-6 fatty acid]] [[arachidonic acid]] and [[glycerol]]. Unlike [[anandamide]], 2-AG is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in rat brain.<ref name="Sug"/><ref name="Kon">Kondo, S., Kondo, H., Nakane, S., et al. 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 Lett 429 152-156 (1998). </ref>  Formation of 2-AG is calcium-dependent and is mediated by the activities of [[phospholipase C]] (PLC) and [[diacylglycerol lipase]] (DAG).<ref name="Sug"/> 2-AG acts as a full agonist at the CB1 receptor.<ref name="Sav">Savinainen, J. R., Jarvinen, T., Laine, K. and Laitinen, J. T. Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar membranes. Br. J. Pharmacol. 134, 664–672(2001).</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="Sug"/> 2-AG is metabolized in vitro by [[monoacylglycerol lipase]] (MGL) and [[fatty acid amide hydrolase]], with MGL likely being the principle metabolizing enzyme in vivo.<ref name="Sav"/>


== References ==
==Discovery==
<references/>
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 |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= 10.1006/bbrc.1995.2437|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, Hanuš 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= 10.1016/0006-2952(95)00109-D|url=http://linkinghub.elsevier.com/retrieve/pii/000629529500109D}}</ref>
*Dinh, T.P., Carpenter, D., Leslie, F.M., et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99(16) 10819-10824 (2002).


==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).<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= 10.1016/S0014-5793(98)00581-X|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.


== External links ==
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>
*[http://www.caymanchem.com/app/template/Product.vm/catalog/62160/promo/searchresult.62160/a/z Caymenchem.com]
 
==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 |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= |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.
 
==See also==
* [[2-Arachidonoyl glyceryl ether]]
 
==References==
=== Footnotes ===
{{Reflist|2}}
 
===General references===
{{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=}}


{{Cannabinoids}}
{{Cannabinoids}}
[[Category:Cannabinoids|Arachidonoylglycerol, 2-]]
{{Neurotransmitters}}
[[Category:Neurotransmitters|Arachidonoylglycerol, 2-]]
 
[[Category:Carboxylate esters|Arachidonoylglycerol, 2-]]
{{DEFAULTSORT:Arachidonoylglycerol, 2-}}
[[Category:Cannabinoids]]
[[Category:Neurotransmitters]]
[[Category:Carboxylate esters]]


[[de:2-Arachidonylglycerol]]
[[it:Arachidonoilglicerolo]]
[[it:Arachidonoilglicerolo]]
[[pl:2-Arachidonyloglicerol]]
[[fi:2-arakidonyyliglyseroli]]
[[fi:2-arakidonyyliglyseroli]]
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{{WikiDoc Sources}}

Latest revision as of 19:28, 27 September 2011

Template:Chembox E number
2-Arachidonoylglycerol
Error creating thumbnail: File missing
Names
IUPAC name
1,3-Dihydroxy-2-propanyl (5Z,8Z,11Z,14Z)-5,8,11,14-eicosatetraenoate
Other names
2-AG, 2-arachidonoylglycerol
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value). Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value).
Properties
C23H38O4
Molar mass 378.3 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor.[1][2] It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol.

Discovery

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,[3][4] 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.[5]

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).[2][6] 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.[7]

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] 2-AG acts as a full agonist at the CB1 receptor.[8] 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] 2-AG is hydrolyzed in vitro by monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH), and the uncharacterized serine hydrolase enzymes ABHD6 and ABHD12.[9] 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.

See also

References

Footnotes

  1. ↑ Stella N, Schweitzer P, Piomelli D (1997). "A second endogenous cannabinoid that modulates long-term potentiation". Nature. 388 (6644): 773–8. doi:10.1038/42015. PMID 9285589. Unknown parameter |month= ignored (help)
  2. ↑ 2.0 2.1 2.2 2.3 Sugiura T, Kodaka T, Nakane S; et al. (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. doi:10.1074/jbc.274.5.2794. PMID 9915812. Unknown parameter |month= ignored (help)
  3. ↑ Sugiura T, Itoh K, Waku K, Hanahan DJ (1994) Proceedings of Japanese conference on the Biochemistry of Lipids, 36, 71-74 (in Japanese)
  4. ↑ Sugiura T, Kondo S, Sukagawa A; et al. (1995). "2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain". Biochem. Biophys. Res. Commun. 215 (1): 89–97. doi:10.1006/bbrc.1995.2437. PMID 7575630. Retrieved 2009-01-27. Unknown parameter |month= ignored (help)
  5. ↑ Mechoulam R, Ben-Shabat S, Hanuš L; et al. (1995). "Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors". Biochemical pharmacology. 50 (1): 83–90. doi:10.1016/0006-2952(95)00109-D. PMID 7605349. Unknown parameter |month= ignored (help)
  6. ↑ Kondo S, Kondo H, Nakane S; et al. (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. doi:10.1016/S0014-5793(98)00581-X. PMID 9650580. Unknown parameter |month= ignored (help)
  7. ↑ Fride E, Bregman T, Kirkham TC. (2005). "Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood" (PDF). Experimental Biology and Medicine. 230 (4): 225–234. doi:10.1371/journal.pbio.0020286. PMID 15792943. Unknown parameter |month= ignored (help)
  8. ↑ Savinainen JR, Järvinen T, Laine K, Laitinen JT (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. PMC 1572991. PMID 11588122. Unknown parameter |month= ignored (help)
  9. ↑ Blankman JL, Simon GM, Cravatt BF (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. PMC 2692834. PMID 18096503. Unknown parameter |month= ignored (help)

General references

Dinh TP, Carpenter D, Leslie FM; et al. (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. PMC 125056. PMID 12136125. Unknown parameter |month= ignored (help)

de:2-Arachidonylglycerol it:Arachidonoilglicerolo fi:2-arakidonyyliglyseroli

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