2-arachidonyl glycerol

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Structural formula
Structure of 2-arachidonylglycerol
General
Surname 2-arachidonyl glycerol
other names
  • 1,3-dihydroxy-2-yl- (5 Z , 8 Z , 11 Z , 14 Z ) -eicosa-5,8,11,14-tetraenoic acid
  • 2-Hydroxy-1- (hydroxymethyl) ethyl ester-5 Z , 8 Z , 11 Z , 14 Z -eicosatetraenoic acid
  • 2-AG
  • 2-Ara-Gl
Molecular formula C 23 H 38 O 4
Brief description

yellow liquid

External identifiers / databases
CAS number 53847-30-6
PubChem 5282280
ChemSpider 4445451
Wikidata Q209320
properties
Molar mass 378.55 g · mol -1
Physical state

liquid

solubility
  • soluble in ethanol and DMSO
  • soluble in acetonitrile
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

2-Arachidonylglycerol ( 2-AG ) is an endocannabinoid that activates the cannabinoid receptors CB 1 and CB 2 . It is the ester made from arachidonic acid and glycerol . It has been found in the brain, liver, lungs, spleen and kidney in rats.

effect

It activates the two well-known cannabinoid receptors. When administered intravenously to mice, they develop the same symptoms as after administration of THC (decreased pain sensation, immobility, decreased spontaneous activity, decreased rectal temperature). It stimulates bone growth by indirectly inhibiting the adrenergic system . and activation of CB 2 receptors. By activating CB 1 receptors, it is neuroprotective in animal models after brain injuries.

pharmacology

Unlike anandamide , it is a full cannabinoid receptor agonist , so 2-AG is believed to be the endogenous ligand of these receptors. It is split into arachidonic acid and glycerol by the enzyme monoglycerolipase (MGL) . In addition, 2-AG acts as a positive allosteric modulator at GABA A receptors .

history

In 1995, Raphael Mechoulam's group at the Hebrew University of Jerusalem in Israel published the discovery of a substance that was isolated from the canine intestine and that binds to cannabinoid receptors. It was found to be identical to synthetic 2-AG.

structure

Despite the chemical differences, it adopts a very similar spatial conformation to tetrahydrocannabinol .

Web links

Individual evidence

  1. ↑ a b c Tocris Bioscience: 2-Arachidonylglycerol MSDS
  2. ↑ Data sheet 2-arachidonyl glycerol, acetonitrile solution, ≈10 mg / mL, ≥98% (HPLC) from Sigma-Aldrich , accessed on November 28, 2012 ( PDF ).
  3. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  4. ↑ S. Kondo, H. Kondo, S. Nakane et al : 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various tiss ratues, and evidence for its generation through CA2 + -dependent and - independent mechanisms . In: FEBS Lett . 429, No. 2, 1998, pp. 152-156. PMID 9650580 .
  5. ↑ Joseph Tam et al .: The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling . In: FASEB journal . tape 22 , no. 1 , 2008, p. 285-294 , doi : 10.1096 / fj.06-7957com , PMID 17704191 .
  6. ^ O. Ofek, M. Karsak, N. Leclerc et al : Peripheral cannabinoid receptor, CB2, regulates bone mass . In: Proc. Natl. Acad. Sci. USA . 103, No. 3, 2006, pp. 696-701. doi : 10.1073 / pnas.0504187103 . PMID 16407142 .
  7. ↑ D. Panikashvili, C. Simeonidou, S. Ben-Shabat et al : An endogenous cannabinoid (2-AG) is neuroprotective after brain injury . In: Nature . 413, No. 6855, 2001, pp. 527-731. doi : 10.1038 / 35097089 . PMID 11586361 .
  8. ↑ T. Sugiura, T. Kodaka, S. Nakane 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 . In: J. Biol. Chem. . 274, No. 5, 1999, pp. 2794-2801. PMID 9915812 .
  9. ↑ TP Dinh, D. Carpenter, FM Leslie et al : Brain monoglyceride lipase participating in endocannabinoid inactivation . In: Proc. Natl. Acad. Sci. USA . 99, No. 16, 2002, pp. 10819-10824. doi : 10.1073 / pnas.152334899 . PMID 12136125 .
  10. ↑ E. Sigel, R. Baur, I. Rácz et al. : The major central endocannabinoid directly acts at GABA (A) receptors . In: Proc. Natl. Acad. Sci. USA . 108, No. 44, 2011, pp. 18150-18155. doi : 10.1073 / pnas.1113444108 . PMID 22025726 . PMC 3207709 (free full text).
  11. ↑ R. Baur, M. Kielar, L. Richter, M. Ernst, GF Ecker, E. Sigel: Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β2 subunit of GABAA receptors . In: J. Neurochem. . 2013. doi : 10.1111 / jnc.12270 . PMID 23600744 .
  12. ^ R. Mechoulam, S. Ben-Shabat, L. Hanus et al : Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors . In: Biochem. Pharmacol. . 50, No. 1, 1995, pp. 83-90. PMID 7605349 .
  13. ↑ J. Barnett-Norris, DP Hurst, DL Lynch, F. Guarnieri, A. Makriyannis, PH Reggio: Conformational memories and the endocannabinoid binding site at the cannabinoid CB1 receptor . In: J. Med. Chem. . 45, No. 17, 2002, pp. 3649-3659. PMID 12166938 .