Biosynthesis of Anandamide and 2-Arachidonoylglycerol

  • Takayuki Sugiura

Anandamide (N-arachidonoylethanolamine) can be synthesized from free arachidonic acid and ethanolamine by the action of a fatty acid amide hydrolase acting in reverse or from preexisting N-arachidonoyl phosphatidylethanolamine by the action of a phosphodiesterase (phospholipase D). Evidence is accumulating that anandamide is synthesized mainly by the latter pathway rather than the former in various mammalian tissues and cells. 2-Arachidonoylglycerol can be synthe sized from arachidonic acid-containing diacylglycerol derived from increased inositol phospholipid metabolism by the action of a diacylglycerol lipase. 2-Arachidonoylglycerol can also be formed via other pathways such as the hydrolysis of the diacylglycerol derived from phosphatidylcholine and phosphatidic acid by the action of a diacylglycerol lipase and the hydrolysis of arachidonic acid- containing lysophosphatidic acid by the action of a phosphatase. The relative importance of these pathways may depend on the types of cells and stimuli. In this review, I have summarized the pathways and enzymes involved in the synthesis of anandamide and 2-arachidonoylglycerol.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahluwalia J, Yaqoob M, Urban L, Bevan S, Nagy I (2003) Activation of capsaicin-sensitive primary sensory neurons induces anandamide production and release. J Neurochem 84:585–591.CrossRefPubMedGoogle Scholar
  2. Basavarajappa BS, Hungund BL (1999) Chronic ethanol increases the cannabinoid receptor agonist anandamide and its precursor N-arachidonoylphosphatidylethanolamine in SK-N-SH cells. J Neurochem 72:522–528.CrossRefPubMedGoogle Scholar
  3. Basavarajappa BS, Saito M, Cooper TB, Hungund BL (2000) Stimulation of cannabinoid receptor agonist 2-arachidonylglycerol by chronic ethanol and its modulation by specific neuromodulators in cerebellar granule neurons. Biochim Biophys Acta 1535:78–86.PubMedGoogle Scholar
  4. Beaulieu P, Bisogno T, Punwar S, Farquhar-Smith WP, Ambrosino G, Di Marzo V, Rice AS (2000) Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat. Eur J Pharmacol 396:85–92.CrossRefGoogle Scholar
  5. Berdyshev EV, Schmid PC, Krebsbach RJ, Schmid HHO (2001) Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells. FASEB J 15:2171–2178.CrossRefPubMedGoogle Scholar
  6. Bisogno T, Maurelli S, Melck D, De Petrocellis L, Di Marzo V (1997a) Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. J Biol Chem 272: 3315–3323.CrossRefPubMedGoogle Scholar
  7. Bisogno T, Sepe N, Melck D, Maurelli S, De Petrocellis L, Di Marzo V (1997b) Biosynthesis, release and degradation of the novel endogenous cannabimimetic metabolite 2-arachidonoylglycerol in mouse neuroblastoma cells. Biochem J 322:671–677.PubMedGoogle Scholar
  8. Bisogno T, Melck D, De Petrocellis L, Di Marzo V (1999) Phosphatidic acid as the biosynthetic precursor of the endocannabinoid 2-arachidonoylglycerol in intact mouse neuroblastoma cells stimulated with ionomycin. J Neurochem 72:2113–2119.CrossRefPubMedGoogle Scholar
  9. Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol 163:463–468.CrossRefPubMedGoogle Scholar
  10. Burstein SH, Hunter SA (1995) Stimulation of anandamide biosynthesis in N-18TG2 neuroblastoma cells by delta 9-tetrahydrocannabinol (THC). Biochem Pharmacol 49:855–858.CrossRefPubMedGoogle Scholar
  11. Burstein SH, Huang SM, Petros TJ, Rossetti RG, Walker JM, Zurier RB (2002) Regulation of anandamide tissue levels by N-arachidonylglycine. Biochem Pharmacol 64:1147–1150.CrossRefPubMedGoogle Scholar
  12. Cadas H, Gaillet S, Beltramo M, Venance L, Piomelli D (1996) Biosynthesis of an endogenous cannabinoid precursor in neurons and its control by calcium and cAMP. J Neurosci 16:3934–3942.PubMedGoogle Scholar
  13. Cadas H, Di Tomaso E, Piomelli D (1997) Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 17:1226–1242.PubMedGoogle Scholar
  14. Carrier EJ, Kearn CS, Barkmeier AJ, Breese NM, Yang W, Nithipatikom K, Pfister SL, Campbell WB, Hillard CJ (2004) Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 65:999–1007.CrossRefPubMedGoogle Scholar
  15. Colodzin M, Bachur NR, Weissbach H, Udenfriend S (1963) Enzymatic formation of fatty acid amides of ethanolamine by rat liver microsomes. Biochem Biophys Res Commun 10:165–171.CrossRefGoogle Scholar
  16. Deutsch DG, Chin SA (1993) Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 46:791–796.CrossRefPubMedGoogle Scholar
  17. Devane WA, Axelrod J (1994) Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes. Proc Natl Acad Sci USA 91:6698–6701.CrossRefPubMedGoogle Scholar
  18. 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
  19. Di S, Boudaba C, Popescu IR, Weng FJ, Harris C, Marcheselli VL, Bazan NG, Tasker JG (2005a) Activity-dependent release and actions of endocannabinoids in the rat hypothalamic supraoptic nucleus. J Physiol 569:751–760.CrossRefPubMedGoogle Scholar
  20. Di S, Malcher-Lopes R, Marcheselli VL, Bazan NG, Tasker JG (2005b) Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology 146:4292–4301.CrossRefPubMedGoogle Scholar
  21. Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691.CrossRefPubMedGoogle Scholar
  22. Di Marzo V, De Petrocellis L, Sepe N, Buono A (1996a) Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells. Biochem J 316:977–984.PubMedGoogle Scholar
  23. Di Marzo V, De Petrocellis L, Sugiura T, Waku K (1996b) Potential biosynthetic connections between the two cannabimimetic eicosanoids, anandamide and 2-arachidonoyl-glycerol, in mouse neuroblastoma cells. Biochem Biophys Res Commun 227:281–288.CrossRefPubMedGoogle Scholar
  24. Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G (1999) Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. Eur J Biochem 264:258–267.CrossRefPubMedGoogle Scholar
  25. Di Marzo V, De Petrocellis L, Bisogno T, Berger A, Mechoulam R (2002) Biology of endocannabinoids. In: Onaivi ES (ed), Biology of Marijuana. Taylor & Francis, London, pp. 125–173.Google Scholar
  26. Edwards DA, Kim J, Alger BE (2006) Multiple mechanisms of endocannabinoid response initiation in hippocampus. J Neurophysiol 95:67–75.CrossRefPubMedGoogle Scholar
  27. Epps DE, Schmid PC, Natarajan V, Schmid HHO (1979) N-Acylethanolamine accumulation in infarcted myocardium. Biochem Biophys Res Commun 90:628–633.CrossRefPubMedGoogle Scholar
  28. Epps DE, Natarajan V, Schmid PC, Schmid HHO (1980) Accumulation of N-acylethanolamine glycerophospholipids in infarcted myocardium. Biochim Biophys Acta 618:420–430.PubMedGoogle Scholar
  29. Franklin A, Parmentier-Batteur S, Walter L, Greenberg DA, Stella N (2003) Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility. J Neurosci 23:7767–7775.PubMedGoogle Scholar
  30. Gammon CM, Allen AC, Morell P (1989) Bradykinin stimulates phosphoinositide hydrolysis and mobilization of arachidonic acid in dorsal root ganglion neurons. J Neurochem 53:95–101.CrossRefPubMedGoogle Scholar
  31. Gauthier KM, Baewer DV, Hittner S, Hillard CJ, Nithipatikom K, Reddy DS, Falck JR, Campbell WB (2005) Endothelium-derived 2-arachidonylglycerol: an intermediate in vasodilatory eicosanoid release in bovine coronary arteries. Am J Physiol Heart Circ Physiol 288:1344–1351.CrossRefGoogle Scholar
  32. Guo Y, Wang H, Okamoto Y, Ueda N, Kingsley PJ, Marnett LJ, Schmid HH, Das SK, Dey SK (2005) N-acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation. J Biol Chem 280:23429–23432.CrossRefPubMedGoogle Scholar
  33. Hansen HS, Lauritzen L, Strand AM, Moesgaard B, Frandsen A (1995) Glutamate stimulates the formation of N-acylphosphatidylethanolamine and N-acylethanolamine in cortical neurons in culture. Biochim Biophys Acta 1258:303–308.PubMedGoogle Scholar
  34. Hansen HH, Ikonomidou C, Bittigau P, Hansen SH, Hansen HS (2001a) Accumulation of the anandamide precursor and other N-acylethanolamine phospholipids in infant rat models of in vivo necrotic and apoptotic neuronal death. J Neurochem 76:39–46.CrossRefPubMedGoogle Scholar
  35. Hansen HH, Schmid PC, Bittigau P, Lastres-Becker I, Berrendero F, Manzanares J, Ikonomidou C, Schmid HHO, Fernandez-Ruiz JJ, Hansen HS (2001b) Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration. J Neurochem 78:1415–1427.CrossRefPubMedGoogle Scholar
  36. Hasegawa-Sasaki H (1985) Early changes in inositol lipids and their metabolites induced by platelet-derived growth factor in quiescent Swiss mouse 3T3 cells. Biochem J 232:99–109.PubMedGoogle Scholar
  37. Hashimotodani Y, Ohno-Shosaku T, Tsubokawa H, Ogata H, Emoto K, Maejima T, Araishi K, Shin HS, Kano M (2005) Phospholipase Cp serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal. Neuron 45:257–268.CrossRefPubMedGoogle Scholar
  38. Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435:1108–1112.CrossRefPubMedGoogle Scholar
  39. Izzo AA, Capasso F, Costagliola A, Bisogno T, Marsicano G, Ligresti A, Matias I, Capasso R, Pinto L, Borrelli F, Cecio A, Lutz B, Mascolo N, Di Marzo V (2003) An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice. Gastroenterology 125:765–774.CrossRefPubMedGoogle Scholar
  40. Jin XH, Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (2007) Discovery and characterization of a Ca2+-independent phosphatidylethanolamine N-acyltransferase generating the anandamide precursor and its congeners. J Biol Chem 282:3614–3623.CrossRefPubMedGoogle Scholar
  41. Jung KM, Mangieri R, Stapleton C, Kim J, Fegley D, Wallace M, Mackie K, Piomelli D (2005) Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors. Mol Pharmacol 68:1196–1202.CrossRefPubMedGoogle Scholar
  42. Kondo S, Kondo H, Nakane S, Kodaka T, Tokumura A, Waku K, Sugiura T (1998a) 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.CrossRefPubMedGoogle Scholar
  43. Kondo S, Sugiura T, Kodaka T, Kudo N, Waku K, Tokumura A (1998b) Accumulation of various N-acylethanolamines including N-arachidonoylethanolamine (anandamide) in cadmium chloride-administered rat testis. Arch Biochem Biophys 354:303–310.CrossRefPubMedGoogle Scholar
  44. Kruszka KK, Gross RW (1994) The ATP- and CoA-independent synthesis of arachidonoylethanolamide. A novel mechanism underlying the synthesis of the endogenous ligand of the cannabinoid receptor. J Biol Chem 269:14345–14348.PubMedGoogle Scholar
  45. Kuwae T, Shiota Y, Schmid PC, Krebsbach R, Schmid HHO (1999) Biosynthesis and turnover of anandamide and other N-acylethanolamines in peritoneal macrophages. FEBS Lett 459:123–127.CrossRefPubMedGoogle Scholar
  46. Liu J, Batkai S, Pacher P, Harvey-White J, Wagner JA, Cravatt BF, Gao B, Kunos G (2003) Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-aB independently of platelet-activating factor. J Biol Chem 278:45034–45039.CrossRefPubMedGoogle Scholar
  47. Liu J, Wang L, Harvey-White J, Osei-Hyiaman D, Razdan R, Gong Q, Chan AC, Zhou Z, Huang BX, Kim HY, Kunos G (2006) A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA 103:13345–13350.CrossRefPubMedGoogle Scholar
  48. Maejima T, Oka S, Hashimotodani Y, Ohno-Shosaku T, Aiba A, Wu D, Waku K, Sugiura T, Kano M (2005) Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phospholipase C-4 signaling cascade in the cerebellum. J Neurosci 25:6826–6835.CrossRefPubMedGoogle Scholar
  49. Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgansberger W, Di Marzo V, Lutz B (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534.CrossRefPubMedGoogle Scholar
  50. McVey DC, Schmid PC, Schmid HHO, Vigna SR (2003) Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1). J Pharmacol Exp Ther 304:713–722.CrossRefPubMedGoogle Scholar
  51. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90.CrossRefPubMedGoogle Scholar
  52. Mechoulam R, Fride E, Ben-Shabat S, Meiri U, Horowitz M (1998a) Carbachol, an acetylcholine receptor agonist, enhances production in rat aorta of 2-arachidonoyl glycerol, a hypotensive endocannabinoid. Eur J Pharmacol 362:1–3.CrossRefGoogle Scholar
  53. Mechoulam R, Fride E, Di Marzo V (1998b) Endocannabinoids. Eur J Pharmacol 359:1–18.CrossRefPubMedGoogle Scholar
  54. Melis M, Perra S, Muntoni AL, Pillolla G, Lutz B, Marsicano G, Di Marzo V, Gessa GL, Pistis M (2004) Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons. J Neurosci 24:10707–10715.CrossRefPubMedGoogle Scholar
  55. Moesgaard B, Petersen G, Jaroszewski JW, Hansen HS (2000) Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain. A 31P NMR and enzyme activity study. J Lipid Res 41:985–990.PubMedGoogle Scholar
  56. Moesgaard B, Petersen G, Mortensen SA, Hansen HS (2002) Substantial species differences in relation to formation and degradation of N-acyl-ethanolamine phospholipids in heart tissue: an enzyme activity study. Comp Biochem Physiol B, Biochem Mol Biol 131:475–482.CrossRefPubMedGoogle Scholar
  57. Morishita J, Okamoto Y, Tsuboi K, Ueno M, Sakamoto H, Maekawa N, Ueda N (2005) Regional distribution and age-dependent expression of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D in rat brain. J Neurochem 94:753–762.CrossRefPubMedGoogle Scholar
  58. Nakane S, Oka S, Arai S, Waku K, Ishima Y, Tokumura A, Sugiura T (2002) 2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing lysophosphatidic acid: occurrence and rapid enzymatic conversion to 2-arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain. Arch Biochem Biophys 402:51–58.CrossRefPubMedGoogle Scholar
  59. Natarajan V, Reddy PV, Schmid PC, Schmid HHO (1982) N-Acylation of ethanolamine phospholipids in canine myocardium. Biochim Biophys Acta 712:342–355.PubMedGoogle Scholar
  60. Natarajan V, Schmid PC, Reddy PV, Zuzarte-Augustin ML, Schmid HHO (1983) Biosynthesis of N-acylethanolamine phospholipids by dog brain preparations. J Neurochem 41:1303–1312.CrossRefPubMedGoogle Scholar
  61. Natarajan V, Schmid PC, Schmid HHO (1986) N-acylethanolamine phospholipid metabolism in normal and ischemic rat brain. Biochim Biophys Acta 878:32–41.PubMedGoogle Scholar
  62. Oka S, Yanagimoto S, Ikeda S, Gokoh M, Kishimoto S, Waku K, Ishima Y, Sugiura T (2005) Evidence for the involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation in mouse ear. J Biol Chem 280:18488–18497.CrossRefPubMedGoogle Scholar
  63. Oka S, Wakui J, Ikeda S, Yanagimoto S, Kishimoto S, Gokoh M, Nasui M, Sugiura T (2006) Involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in oxazolone-induced contact dermatitis in mice. J Immunol 177:8796–8805.PubMedGoogle Scholar
  64. Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (2004) Molecular characterization of a phospholipase D generating anandamide and its congeners. J Biol Chem 279:5298–5305.CrossRefPubMedGoogle Scholar
  65. Okamoto Y, Morishita J, Wang J, Schmid PC, Krebsbach RJ, Schmid HH, Ueda N (2005) Mammalian cells stably overexpressing N-acylphosphatidylethanolamine-hydrolysing phospholipase D exhibit significantly decreased levels of N-acylphosphatidylethanolamines. Biochem J 389:241–247.CrossRefPubMedGoogle Scholar
  66. Panikashvili D, Simeonidou C, Ben-Shabat S, Hanus L, Breuer A, Mechoulam R, Shohami E (2001) An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 413:527–531.CrossRefPubMedGoogle Scholar
  67. Pestonjamasp VK, Burstein SH (1998) Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system. Biochim Biophys Acta 1394:249–260.PubMedGoogle Scholar
  68. Petersen G, Hansen HS (1999) N-acylphosphatidylethanolamine-hydrolysing phospholipase D lacks the ability to transphosphatidylate. FEBS Lett 455:41–44.CrossRefPubMedGoogle Scholar
  69. Piomelli D, Beltramo M, Giuffrida A, Stella N (1998) Endogenous cannabinoid signaling. Neurobiol Dis 5:462–473.CrossRefPubMedGoogle Scholar
  70. Prescott SM, Majerus PW (1983) Characterization of 1, 2-diacylglycerol hydrolysis in human platelets. Demonstration of an arachidonoyl-monoacylglycerol intermediate. J Biol Chem 258:764–769.PubMedGoogle Scholar
  71. Rademacher DJ, Patel S, Ho WS, Savoie AM, Rusch NJ, Gauthier KM, Hillard CJ (2005) U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance. Am J Physiol Heart Circ Physiol 288:H2694–2701.CrossRefPubMedGoogle Scholar
  72. Safo PK, Regehr WG (2005) Endocannabinoids control the induction of cerebellar LTD. Neuron 48:647–659.CrossRefPubMedGoogle Scholar
  73. Schmid PC, Reddy PV, Natarajan V, Schmid HHO (1983) Metabolism of N-acylethanolamine phospholipids by a mammalian phosphodiesterase of the phospholipase D type. J Biol Chem 258:9302–9306.PubMedGoogle Scholar
  74. Schmid HHO, Schmid PC, Natarajan V (1990) N-acylated glycerophospholipids and their derivatives. Prog Lipid Res 29:1–43.CrossRefPubMedGoogle Scholar
  75. Stella N, Piomelli D (2001) Receptor-dependent formation of endogenous cannabinoids in cortical neurons. Eur J Pharmacol 425:189–196.CrossRefPubMedGoogle Scholar
  76. Stella N, Schweitzer P, Piomelli D (1997) A second endogenous cannabinoid that modulates long-term potentiation. Nature 388:773–778.CrossRefPubMedGoogle Scholar
  77. Straiker A, Mackie K (2005) Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones. J Physiol 569:501–517.CrossRefPubMedGoogle Scholar
  78. Sugiura T, Waku K (2000) 2-Arachidonoylglycerol and the cannabinoid receptors. Chem Phys Lipids 108:89–106.CrossRefPubMedGoogle Scholar
  79. 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
  80. Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Waku K (1996a) Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca2+-dependent transacylase and phosphodiesterase activities. Biochem Biophys Res Commun 218:113–117.CrossRefPubMedGoogle Scholar
  81. Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Ishima Y, Waku K (1996b) Transacylase-mediated and phosphodiesterase-mediated synthesis of N-arachidonoylethanolamine, an endogenous cannabinoid-receptor ligand, in rat brain microsomes. Comparison with synthesis from free arachidonic acid and ethanolamine. Eur J Biochem 240:53–62.PubMedCrossRefGoogle Scholar
  82. Sugiura T, Kodaka T, Nakane S, Kishimoto S, Kondo S, Waku K (1998) Detection of an endogenous cannabimimetic molecule, 2-arachidonoylglycerol, and cannabinoid CB1 receptor mRNA in human vascular cells: is 2-arachidonoylglycerol a possible vasomodulator? Biochem Biophys Res Commun 243:838–843.CrossRefPubMedGoogle Scholar
  83. Sugiura T, Yoshinaga N, Kondo S, Waku K, Ishima Y (2000) Generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain. Biochem Biophys Res Commun 271:654–658.CrossRefPubMedGoogle Scholar
  84. Sugiura T, Yoshinaga N, Waku K (2001) Rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain after decapitation. Neurosci Lett 297:175–178.CrossRefPubMedGoogle Scholar
  85. Sugiura T, Kishimoto S, Oka S, Gokoh M (2006a) Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog Lipid Res 45:405–446.CrossRefPubMedGoogle Scholar
  86. Sugiura T, Oka S, Ikeda S, Waku K (2006b) Occurrence, biosynthesis, and metabolism of endocannabinoid. In: Onaivi ES, Sugiura T, Di Marzo V (eds), Endocannabinoids: The Brain and Body’s Marijuana and Beyond. Taylor & Francis, Boca Raton, pp. 177–214.Google Scholar
  87. Tsutsumi T, Kobayashi T, Ueda H, Yamauchi E, Watanabe S, Okuyama H (1994) Lysophosphoinositide-specific phospholipase C in rat brain synaptic plasma membranes. Neurochem Res 19:399–406.CrossRefPubMedGoogle Scholar
  88. Ueda N, Kurahashi Y, Yamamoto S, Tokunaga T (1995) Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. J Biol Chem 270:23823–23827.CrossRefPubMedGoogle Scholar
  89. Varga K, Wagner JA, Bridgen DT, Kunos G (1998) Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 12:1035–1044.PubMedGoogle Scholar
  90. Wagner JA, Varga K, Ellis EF, Rzigalinski BA, Martin BR, Kunos G (1997) Activation of peripheral CB1 cannabinoid receptors in haemorrhagic shock. Nature 390:518–521.CrossRefPubMedGoogle Scholar
  91. Walker JM, Huang SM, Strangman NM, Tsou K, Sanudo-Pena MC (1999) Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci USA 96:12198–12203.CrossRefPubMedGoogle Scholar
  92. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ (2003) The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 307:129–137.CrossRefPubMedGoogle Scholar
  93. Walter L, Stella N (2003) Endothelin-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes. Glia 44:85–90.CrossRefPubMedGoogle Scholar
  94. Walter L, Franklin A, Witting A, Moller T, Stella N (2002) Astrocytes in culture produce anandamide and other acylethanolamides. J Biol Chem 277:20869–20876.CrossRefPubMedGoogle Scholar
  95. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405.PubMedGoogle Scholar
  96. Walter L, Dinh T, Stella N (2004) ATP induces a rapid and pronounced increase in 2-arachidonoylglycerol production by astrocytes, a response limited by monoacylglycerol lipase. J Neurosci 24:8068–8074.CrossRefPubMedGoogle Scholar
  97. Wang J, Okamoto Y, Morishita J, Tsuboi K, Miyatake A, Ueda N (2006) Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-p-lactamase family. J Biol Chem 281:12325–12335.CrossRefPubMedGoogle Scholar
  98. Witting A, Walter L, Wacker J, Moller T, Stella N (2004) P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Proc Natl Acad Sci USA 101:3214–3219.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Takayuki Sugiura
    • 1
  1. 1.Teikyo UniversitySagamikoJapan

Personalised recommendations