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Other Cannabimimetic Lipid Signaling Molecules

  • Heather B. Bradshaw

The endogenous lipids anandamide and 2-arachidonoylglycerol (2-AG) play predominant signaling roles through G protein-coupled receptors (GPCRs) and at least one transient receptor potential channel (TRP). Additional structurally similar lipid signaling molecules that have cannabinoid-like (cannabimimetic) activity in which they produce similar cellular, physiological, and behavioral phenotypes as anandamide and 2-AG have recently been discovered. Like the endogenous cannabinoids, many of the actions of these structurally similar endogenous lipids are known to occur through both GPCRs and TRPs. The cannabimimetic lipid signaling molecules of N-arachidonoyl glycine, N-arachidonoyl dopamine, N-arachidonoyl serine, the family of N-acyl ethanolamines, and 2-acyl glycerols and their roles in cellular signaling and physiology are discussed here.

Keywords

Glyceryl Ether Prostaglandin Leukot Essent Fatty Acid Lipid Signaling Molecule Carbon Saturated Fatty Acid Noladin Ether 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahern GP (2003) Activation of TRPV1 by the satiety factor oleoylethanolamide. J Biol Chem 278:30429–30434.CrossRefPubMedGoogle Scholar
  2. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, Bisogno T, De Petrocellis L, Di Marzo V, Mechoulam R (1998) An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur J Pharmacol 353:23–31.CrossRefPubMedGoogle Scholar
  3. Berdyshev EV (1999) Inhibition of sea urchin fertilization by fatty acid ethanolamides and cannabinoids. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 122:327–330.CrossRefPubMedGoogle Scholar
  4. Bisogno T, Sepe N, Melck D, Maurelli S, De Petrocellis L, Di Marzo V (1997) Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells. Biochem J 322:671–677.PubMedGoogle Scholar
  5. Burstein SH, Rossetti RG, Yagen B, Zurier RB (2000) Oxidative metabolism of anandamide. Prostaglandins Other Lipid Mediat 61:29–41.CrossRefPubMedGoogle Scholar
  6. Butelman ER, Ball JW, Harris TJ, Kreek MJ (2003) Topical capsaicin-induced allodynia in unanesthetized primates: pharmacological modulation. J Pharmacol Exp Ther 306:1106–1114.CrossRefPubMedGoogle Scholar
  7. Calignano A, La Rana G, Giuffrida A, Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277–281.CrossRefPubMedGoogle Scholar
  8. Calignano A, La Rana G, Piomelli D (2001) Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol 419:191–198.CrossRefPubMedGoogle Scholar
  9. Darmani NA, Izzo AA, Degenhardt B, Valenti M, Scaglione G, Capasso R, Sorrentini I, Di Marzo V (2005) Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: review of the available pre-clinical data, and first human studies. Neuropharmacology 48:1154–1163.CrossRefPubMedGoogle Scholar
  10. De Petrocellis L, Bisogno T, Maccarrone M, Davis JB, Finazzi-Agro A, Di Marzo V (2001) The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. J Biol Chem 276:12856–12863.CrossRefPubMedGoogle Scholar
  11. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949.CrossRefPubMedGoogle Scholar
  12. Di Marzo V, De Petrocellis L, Sepe N, Buono A (1996) Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells. Biochem J 316:977–984.PubMedGoogle Scholar
  13. Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA 92:3376–3380.CrossRefPubMedGoogle Scholar
  14. 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 513:294–298.CrossRefPubMedGoogle Scholar
  15. Fride E, Ginzburg Y, Breuer A, Bisogno T, Di Marzo V, Mechoulam R (2001) Critical role of the endogenous cannabinoid system in mouse pup suckling and growth. Eur J Pharmacol 419:207–214.CrossRefPubMedGoogle Scholar
  16. Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425:90–93.CrossRefPubMedGoogle Scholar
  17. Fu J, Astarita G, Gaetani S, Kim J, Cravatt BF, Mackie K, Piomelli D (2007) Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine. J Biol Chem 282:1518–1528.CrossRefPubMedGoogle Scholar
  18. Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, Edenson S, Zhang TJ, Viswanadhan VN, Toth A, Pearce LV, Vanderah TW, Porreca F, Blumberg PM, Lile J, Sun Y, Wild K, Louis JC, Treanor JJ (2004) Molecular determinants of vanilloid sensitivity in TRPV1. J Biol Chem 279:20283–20295.CrossRefPubMedGoogle Scholar
  19. Gomez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, Cippitelli A, Nava F, Piomelli D, Rodriguez de Fonseca F (2002) A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22:9612–9617.PubMedGoogle Scholar
  20. Guzman M, Lo Verme J, Fu J, Oveisi F, Blazquez C, Piomelli D (2004) Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-,). J Biol Chem 279:27849–27854.CrossRefPubMedGoogle Scholar
  21. Hanus L, Gopher A, Almog S, Mechoulam R (1993) Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. J Med Chem 36:3032–3034.CrossRefPubMedGoogle Scholar
  22. Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R (2001) 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98:3662–3665.CrossRefPubMedGoogle Scholar
  23. Harrison S, De Petrocellis L, Trevisani M, Benvenuti F, Bifulco M, Geppetti P, Di Marzo V (2003) Capsaicin-like effects of N-arachidonoyl-dopamine in the isolated guinea pig bronchi and urinary bladder. Eur J Pharmacol 475:107–114.CrossRefPubMedGoogle Scholar
  24. Huang SM, Walker JM (2006) Enhancement of spontaneous and heat-evoked activity in spinal nociceptive neurons by the endovanilloid/endocannabinoid N-arachidonoyldopamine (NADA). J Neurophysiol 95:1207–1212.CrossRefPubMedGoogle Scholar
  25. Huang SM, Bisogno T, Petros TJ, Chang SY, Zavitsanos PA, Zipkin RE, Sivakumar R, Coop A, Maeda DY, De Petrocellis L, Burstein S, Di Marzo V, Walker JM (2001) Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain. J Biol Chem 276:42639–42644.CrossRefPubMedGoogle Scholar
  26. Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99:8400–8405.CrossRefPubMedGoogle Scholar
  27. Ikeda Y, Iguchi H, Nakata M, Ioka RX, Tanaka T, Iwasaki S, Magoori K, Takayasu S, Yamamoto TT, Kodama T, Yada T, Sakurai T, Yanagisawa M, Sakai J (2005) Identification of N-arachidonylglycine, U18666A, and 4-androstene-3, 17-dione as novel insulin Secretagogues. Biochem Biophys Res Commun 333:778–786.CrossRefPubMedGoogle Scholar
  28. Jaggar SI, Sellaturay S, Rice AS (1998) The endogenous cannabinoid anandamide, but not the CB2 ligand palmitoylethanolamide, prevents the viscero-visceral hyper-reflexia associated with inflammation of the rat urinary bladder. Neurosci Lett 253:123–126.CrossRefPubMedGoogle Scholar
  29. Karava V, Fasia L, Siafaka-Kapadai A (2001) Anandamide amidohydrolase activity, released in the medium by Tetrahymena pyriformis. Identification and partial characterization. FEBS Lett 508:327–331.CrossRefPubMedGoogle Scholar
  30. Kohno M, Hasegawa H, Inoue A, Muraoka M, Miyazaki T, Oka K, Yasukawa M (2006) Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18. Biochem Biophys Res Commun 347:827–832.CrossRefPubMedGoogle Scholar
  31. Kuehl FA, Jacob TA, Ganley OH, Ormond RE, Meisinger MAP (1957) The identification of N-3(hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent. J Am Chem Soc 79:5577–5578.CrossRefGoogle Scholar
  32. Laine K, Jarvinen K, Mechoulam R, Breuer A, Jarvinen 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 43:3216–3222.PubMedGoogle Scholar
  33. Lambert DM, Di Marzo V (1999) The palmitoylethanolamide and oleamide enigmas: are these two fatty acid amides cannabimimetic? Curr Med Chem 6:757–773.PubMedGoogle Scholar
  34. Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ (2002) The palmitoylethanolamide family: a new class of anti-inflammatory agents? Curr Med Chem 9:663–674.PubMedGoogle Scholar
  35. Maccarrone M, van der Stelt M, Rossi A, Veldink GA, Vliegenthart JF, Agro AF (1998) Anandamide hydrolysis by human cells in culture and brain. J Biol Chem 273:32332–32339.CrossRefPubMedGoogle Scholar
  36. Maccarrone M, Attina M, Bari M, Cartoni A, Ledent C, Finazzi-Agro A (2001a) Anandamide degradation and N-acylethanolamines level in wild-type and CB1 cannabinoid receptor knockout mice of different ages. J Neurochem 78:339–348.CrossRefPubMedGoogle Scholar
  37. Maccarrone M, Bari M, Battista N, Di Rienzo M, Finazzi-Agro A (2001b) Endogenous cannabinoids in neuronal and immune cells: toxic effects, levels and degradation. Funct Neurol 16:53–60.PubMedGoogle Scholar
  38. Maurelli S, Bisogno T, De Petrocellis L, Di Luccia A, Marino G, Di Marzo V (1995) Two novel classes of neuroactive fatty acid amides are substrates for mouse neuroblastoma ‘anandamide amidohydrolase’. FEBS Lett 377:82–86.CrossRefPubMedGoogle Scholar
  39. Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A (1996) N-(2-hydroxyethyl) hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol 300:227–236.CrossRefPubMedGoogle Scholar
  40. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90.CrossRefPubMedGoogle Scholar
  41. Milman G, Maor Y, Abu-Lafi S, Horowitz M, Gallily R, Batkai S, Mo FM, Offertaler L, Pacher P, Kunos G, Mechoulam R (2006) N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties. Proc Natl Acad Sci USA 103:2428–2433.CrossRefPubMedGoogle Scholar
  42. Oka S, Tsuchie A, Tokumura A, Muramatsu M, Suhara Y, Takayama H, Waku K, Sugiura T (2003) Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species. J Neurochem 85:1374–1381.CrossRefPubMedGoogle Scholar
  43. Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, Jackson HC, Procter MJ, Rasamison CM, Tang-Christensen M, Widdowson PS, Williams GM, Reynet C (2006) Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 3:167–175.CrossRefPubMedGoogle Scholar
  44. Premkumar LS, Qi ZH, Van Buren J, Raisinghani M (2004) Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of vanilloid receptor. J Neurophysiol 91:1442–1449.CrossRefPubMedGoogle Scholar
  45. Prusakiewicz JJ, Kingsley PJ, Kozak KR, Marnett LJ (2002) Selective oxygenation of N-arachidonylglycine by cyclooxygenase-2. Biochem Biophys Res Commun 296:612–617.CrossRefPubMedGoogle Scholar
  46. Rakhshan F, Day TA, Blakely RD, Barker EL (2000) Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells. J Pharmacol Exp Ther 292:960–967.PubMedGoogle Scholar
  47. 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 360:216–226.CrossRefPubMedGoogle Scholar
  48. Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo L, Nava F, Fu J, Murillo-Rodriguez E, Giuffrida A, LoVerme J, Gaetani S, Kathuria S, Gall C, Piomelli D (2001) An anorexic lipid mediator regulated by feeding. Nature 414:209–212.CrossRefPubMedGoogle Scholar
  49. Sagar DR, Smith PA, Millns PJ, Smart D, Kendall DA, Chapman V (2004) TRPV1 and CB1 receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat. Eur J Neurosci 20:175–184.CrossRefPubMedGoogle Scholar
  50. Salzet M, Stefano GB (2002) The endocannabinoid system in invertebrates. Prostaglandins Leukot Essent Fatty Acids 66:353–361.CrossRefPubMedGoogle Scholar
  51. Sancho R, Macho A, de La Vega L, Calzado MA, Fiebich BL, Appendino G, Munoz E (2004) Immunosuppressive activity of endovanilloids: N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways. J Immunol 172:2341–2351.PubMedGoogle Scholar
  52. Schmid HH, Berdyshev EV (2002) Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides: metabolism and function. Prostaglandins Leukot Essent Fatty Acids 66:363–376.CrossRefPubMedGoogle Scholar
  53. Schuel H, Burkman LJ, Lippes J, Crickard K, Forester E, Piomelli D, Giuffrida A (2002) N-Acylethanolamines in human reproductive fluids. Chem Phys Lipids 121:211–227.CrossRefPubMedGoogle Scholar
  54. Sheskin T, Hanus L, Slager J, Vogel Z, Mechoulam R (1997) Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor. J Med Chem 40:659–667.CrossRefPubMedGoogle Scholar
  55. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97.CrossRefPubMedGoogle Scholar
  56. Toth A, Kedei N, Wang Y, Blumberg PM (2003) Arachidonyl dopamine as a ligand for the vanilloid receptor VR1 of the rat. Life Sci 73:487–498.CrossRefPubMedGoogle Scholar
  57. Wiles AL, Pearlman RJ, Rosvall M, Aubrey KR, Vandenberg RJ (2006) N-Arachidonyl-glycine inhibits the glycine transporter, GLYT2a. J Neurochem 99:781–786.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Heather B. Bradshaw
    • 1
  1. 1.Psychological and Brain Sciences, The Kinsey Institute for Research in Sex, Gender and ReproductionIndiana University Bloomington

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