2-Arachidonyl glyceryl ether

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2-Arachidonyl glyceryl ether
Names
IUPAC names
2-[(5Z,8Z,11Z,14Z)-5,8,11,14- Icosatetraen-
1-yloxy]-1,3-propanediol
Other names
2-AGE, 2-arachidonylglyceryl ether, Noladin ether, Noladin
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
  • InChI=1S/C23H40O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-26-23(21-24)22-25/h6-7,9-10,12-13,15-16,23-25H,2-5,8,11,14,17-22H2,1H3/b7-6-,10-9-,13-12-,16-15- checkY
    Key: CUJUUWXZAQHCNC-DOFZRALJSA-N checkY
  • InChI=1/C23H40O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-26-23(21-24)22-25/h6-7,9-10,12-13,15-16,23-25H,2-5,8,11,14,17-22H2,1H3/b7-6-,10-9-,13-12-,16-15-
    Key: CUJUUWXZAQHCNC-DOFZRALJBH
  • OCC(OCCCC\C=C/C/C=C\C\C=C/C\C=C/CCCCC)CO
Properties
C23H40O3
Molar mass 364.56 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

2-Arachidonyl glyceryl ether (2-AGE, Noladin ether) is a putative endocannabinoid discovered by Lumír Hanuš and colleagues at the Hebrew University of Jerusalem, Israel. Its isolation from porcine brain and its structural elucidation and synthesis were described in 2001.[1]

Discovery

Lumír Hanuš, Saleh Abu-Lafi, Ester Fride, Aviva Breuer, Zvi Vogel, Deborah E. Shalev, Irina Kustanovich, and Raphael Mechoulam found the endogenous agonist of the cannabinoid receptor type 1 (CB1) in 2000. The discovery was 100 gram of porcine brain, (approximately a single brain) was added to a mixture of 200 mL of chloroform and 200 mL of methanol and mixed in a laboratory blender for 2 minutes. 100 mL of Water was then added, and the mixing process continued for another minute. After this, the mixture was filtered. Two layers then formed and the layer of water-methanol was separated and evaporated when pressure was reduced. Synaptosomal membranes were prepared from 250g of the brains of Sabra male rats. A Hewlett Packard G 1800B GCD system that has a HP-5971 GC with electron ionization detector was used.[1]

Production

The production of the endocannabinoid is enhanced in normal, but not in endothelium-denuded rat aorta on reacting with carbachol, an parasympathomimetic drug. It potently reduces blood pressure in rats and may represent an endothelium-derived hypotension factor.[1]

2-Arachidonyl glyceryl ether's structure can be determined by mass spectrometry and Rutherford backscattering spectrometry. It was confirmed by comparison with a synthetic sample of the endocannabinoid. It binds to the Cannabinoid receptor type 1 (Ki = 21.2 ± 0.5 nM), which causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice.[1] The endocannabinoid exhibits Ki values of 21.2 nM and >3 µM at the Cannabinoid receptor type 1 and the peripheral cannabinoid receptors.[2]

The presence of 2-AGE in body tissue is disputed. Although a research group from Teikyo University, Kanagawa, Japan could not detect it in the brains of mice, hamsters, guinea-pigs or pigs,[3] two other research groups successfully detected it in animal tissues.[4][5]

Pharmacology

2-AGE binds with a Ki of 21 nM to the CB1 receptor[1] and 480 nM to the CB2 receptor.[6] It shows agonistic behaviour on both receptors and is a partial agonist for the TRPV1 channel.[7] After binding to CB2 receptors it inhibits adenylate cyclase and stimulates ERK-MAPK and regulates calcium transients.[8] In comparison to 2-arachidonoyl glycerol, noladin is metabolically more stable resulting in a longer half-life.[9] It lowers Intraocular pressure,[9] increases the uptake of GABA in the globus pallidus of rats[10] and is neuroprotective by binding to and activation of PPARα.[11]

See also

References

  1. ^ a b c d e Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11259648, please use {{cite journal}} with |pmid=11259648 instead.
  2. ^ "2-Arachidonyl Glycerol ether · Noladin; 2-AG ether (CAS 222723-55-9) || Cayman Chemical". Cayman Chemical. Retrieved 2011-05-29.
  3. ^ Oka S; Tsuchie A; Tokumura A; et al. (2003). "Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species". J. Neurochem. 85 (6): 1374–81. doi:10.1046/j.1471-4159.2003.01804.x. PMID 12787057. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  4. ^ Fezza F, Bisogno T, Minassi A, Appendino G, Mechoulam R, Di Marzo V (2002). "Noladin ether, a putative novel endocannabinoid: inactivation mechanisms and a sensitive method for its quantification in rat tissues". FEBS Lett. 513 (2–3): 294–8. doi:10.1016/S0014-5793(02)02341-4. PMID 11904167.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Richardson D, Ortori CA, Chapman V, Kendall DA, Barrett DA (2007). "Quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography-tandem electrospray ionization mass spectrometry". Anal. Biochem. 360 (2): 216–26. doi:10.1016/j.ab.2006.10.039. PMID 17141174.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Shoemaker JL, Joseph BK, Ruckle MB, Mayeux PR, Prather PL (2005). "The endocannabinoid noladin ether acts as a full agonist at human CB2 cannabinoid receptors". J. Pharmacol. Exp. Ther. 314 (2): 868–75. doi:10.1124/jpet.105.085282. PMID 15901805.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Duncan M, Millns P, Smart D, Wright JE, Kendall DA, Ralevic V (2004). "Noladin ether, a putative endocannabinoid, attenuates sensory neurotransmission in the rat isolated mesenteric arterial bed via a non-CB1/CB2 Gi/o linked receptor". Br. J. Pharmacol. 142 (3): 509–18. doi:10.1038/sj.bjp.0705789. PMC 1574960. PMID 15148262.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Shoemaker JL, Ruckle MB, Mayeux PR, Prather PL (2005). "Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors". J. Pharmacol. Exp. Ther. 315 (2): 828–38. doi:10.1124/jpet.105.089474. PMID 16081674.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ a b Laine K, Järvinen K, Mechoulam R, Breuer A, Järvinen T (2002). "Comparison of the enzymatic stability and intraocular pressure effects of 2-arachidonylglycerol and noladin ether, a novel putative endocannabinoid". Invest. Ophthalmol. Vis. Sci. 43 (10): 3216–22. PMID 12356827.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Venderova K, Brown TM, Brotchie JM (2005). "Differential effects of endocannabinoids on [(3)H]-GABA uptake in the rat globus pallidus". Exp. Neurol. 194 (1): 284–7. doi:10.1016/j.expneurol.2005.02.012. PMID 15899265.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Sun Y; Alexander SP; Garle MJ; et al. (2007). "Cannabinoid activation of PPARα; a novel neuroprotective mechanism". Br. J. Pharmacol. 152 (5): 734–43. doi:10.1038/sj.bjp.0707478. PMC 2190030. PMID 17906680. {{cite journal}}: Unknown parameter |author-separator= ignored (help)

External links

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