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Endocannabinoids: synthesis and degradation

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Book cover Reviews of Physiology Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 160))

Abstract

Endocannabinoids were defined in 1995 as endogenous agonists of cannabinoid receptors, i.e. of the G protein-coupled receptors for cannabis's psychoactive principle, Δ9-tetrahydrocannabinol. Although there appear to be several endocannabinoids, only two of such endogenous mediators have been thoroughly studied so far: anandamide and 2-arachidonoylglycerol (2-AG). A general strategy seems to apply to the biosynthesis and degradation of anandamide and 2-AG, although the levels of these two compounds appear to be regulated in different, and sometimes even opposing, ways. “Endocannabinoid enzymes”, that is to say enzymes that catalyse endocannabinoid biosynthesis or degradation, have been identified and in some cases cloned, and will be described in this review together with their possible pharmacological targeting for therapeutic purposes. The cellular and subcellular localization and the modes for the regulation of the expression and activity of these enzymes play an important role in the functions played by the endocannabinoids under physiological and pathological conditions.

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References

  • Arreaza G, Devane WA, Omeir RL, Sajnani G, Kunz J, Cravatt BF, Deutsch DG (1997) The cloned rat hydrolytic enzyme responsible for the breakdown of anandamide also catalyzes its formation via the condensation of arachidonic acid and ethanolamine. Neurosci Lett 234:59–62

    PubMed  CAS  Google Scholar 

  • Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302

    PubMed  CAS  Google Scholar 

  • Basavarajappa BS, Saito M, Cooper TB, Hungund BL (2003) Chronic ethanol inhibits the anandamide transport and increases extracellular anandamide levels in cerebellar granule neurons. Eur J Pharmacol 466:73–83

    PubMed  CAS  Google Scholar 

  • Batkai S, Pacher P, Osei-Hyiaman D, Radeva S, Liu J, Harvey-White J, Offertaler L, Macie K, Rudd MA, Bukoski RD, Kunos G (2004) Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 110:1996–2002

    PubMed  CAS  Google Scholar 

  • Beltramo M, Piomelli D (2000) Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2-arachidonylglycerol. Neuroreport 11:1231–1235

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Berdyshev EV, Schmid PC, Krebsbach RJ, Schmid HH (2001) Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells. FASEB J 15:2171–2178

    PubMed  CAS  Google Scholar 

  • Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V (2001) Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets. Proc Natl Acad Sci USA 98:6402–6406

    PubMed  CAS  Google Scholar 

  • Berrendero F, Sepe N, Ramos JA, Di Marzo V, Fernandez-Ruiz JJ (1999) Analysis of cannabinoid receptor binding and mRNA expression and endogenous cannabinoid contents in the developing rat brain during late gestation and early postnatal period. Synapse 33:181–191

    PubMed  CAS  Google Scholar 

  • Bifulco M, Laezza C, Valenti M, Ligresti A, Portella G, Di Marzo V (2004) A new strategy to block tumor growth by inhibiting endocannabinoid inactivation. FASEB J 18:1606–1608

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Bisogno T, Melck D, De Petrocellis L, Bobrov My, Gretskaya NM, Bezuglov VV, Sitachitta N, Gerwick WH, Di Marzo V (1998) Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. Biochem Biophys Res Commun 248:515–522

    PubMed  CAS  Google Scholar 

  • Bisogno T, Berrendero F, Ambrosino G, Cebeira M, Ramos JA, Fernandez-Ruiz JJ, Di Marzo V (1999a) Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 256:377–380

    PubMed  CAS  Google Scholar 

  • Bisogno T, Melck D, De Petrocellis L, Di Marzo V (1999b) Phosphatidic acid as the biosynthetic precursor of the endocannabinoid 2-arachidonoylglycerol in intact mouse neuroblastoma cells stimulated with ionomycin. J Neurochem 72:2113–2119

    PubMed  CAS  Google Scholar 

  • Bisogno T, Melck D, Bobrov MYu, Gretskaya NM, Bezuglov VV, De Petrocellis L, Di Marzo V (2000) N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem J 3:817–824

    Google Scholar 

  • Bisogno T, Maccarrone M, De Petrocellis L, Jarrahian A, Finazzi-Agro A, Hillard C, Di Marzo V (2001) The uptake by cells of 2-arachidonoylglycerol, an endogenous agonist of cannabinoid receptors. Eur J Biochem 268:1982–1989

    PubMed  CAS  Google Scholar 

  • Bisogno T, De Petrocellis L, Di Marzo V (2002) Fatty acid amide hydrolase, an enzyme with many bioactive substrates. Possible therapeutic implications. Curr Pharm Des 8:533–547

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Bisogno T, Ligresti A, Di Marzo V (2005a) The endocannabinoid signalling system: biochemical aspects. Pharmacol Biochem Behav 81:224–238

    PubMed  CAS  Google Scholar 

  • Bisogno T, Maione S, Valenti M, et al (2005b) FAAH inhibition elevates endocannabinoid levels in the periaqueductal grey of the rat: dual effects on nociception via CB1 and TRPV1 receptors. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24–27 June 2005. International Cannabinoid Research Society, Burlington, p 34

    Google Scholar 

  • Bojesen IN, Hansen HS (2003) Binding of anandamide to bovine serum albumin. J Lipid Res 44:1790–1794

    PubMed  CAS  Google Scholar 

  • Bracey MH, Hanson MA, Masuda KR, Stevens RC, Cravatt BF (2002) Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science 298:1793–1796

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Capasso R, Matias I, Lutz B, Borrelli F, Capasso F, Marsicano G, Mascolo N, Monory K, Valenti M, Di Marzo V, Izzo AA (2005) Fatty acid amide hydrolase controls mouse intestinal motility in vivo. Gastroenterology 129:941–951

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Chesterfield AK, Moore SA, Schober DA, et al (2005) Pharmacological characterization of the endocannabinoid transporter using a novel high affinity ligand. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24–27 June 2005. International Cannabinoid Research Society, Burlington, p 9

    Google Scholar 

  • Chevaleyre V, Castillo PE (2003) Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. Neuron 38:461–472

    PubMed  CAS  Google Scholar 

  • Cohen C, Perrault G, Voltz C, Steinberg R, Soubrie P (2002) SR141716, a central cannabinoid [CB(1)] receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 13:451–463

    PubMed  CAS  Google Scholar 

  • Craib SJ, Ellington HC, Pertwee RG, Ross RA (2001) A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus. Br J Pharmacol 134:30–37

    PubMed  CAS  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384:83–87

    PubMed  CAS  Google Scholar 

  • Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, Lichtman AH (2001) Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98:9371–9376

    PubMed  CAS  Google Scholar 

  • Cravatt BF, Saghatelian A, Hawkins EG, Clement AB, Bracey MH, Lichtman AH (2004) Functional disassociation of the central and peripheral fatty acid amide signaling systems. Proc Natl Acad Sci USA 101:10821–10826

    PubMed  CAS  Google Scholar 

  • de Lago E, Petrosino S, Valenti M, Morera E, Ortega-Gutierrez S, Fernandez-Ruiz J, Di Marzo V (2005) Effect of repeated systemic administration of selective inhibitors of endocannabinoid inactivation on rat brain endocannabinoid levels. Biochem Pharmacol 70:446–452

    PubMed  Google Scholar 

  • De Petrocellis L, Cascio MG, Di Marzo V (2004) The endocannabinoid system: a general view and latest additions. Br J Pharmacol 141:765–774

    PubMed  Google Scholar 

  • De Vries TJ, Shaham Y, Homberg JR, Crombag H, Schuurman K, Dieben J, Vanderschuren LJ, Schoffelmeer AN (2001) A cannabinoid mechanism in relapse to cocaine seeking. Nat Med 7:1151–1154

    PubMed  Google Scholar 

  • Deutsch DG, Chin SA (1993) Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 46:791–796

    PubMed  CAS  Google Scholar 

  • Deutsch DG, Ueda N, Yamamoto S (2002) The fatty acid amide hydrolase (FAAH). Prostaglandins Leukot Essent Fatty Acids 66:201–210

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Di Marzo V, Fontana A (1995) Anandamide, an endogenous cannabinomimetic eicosanoid: ‘killing two birds with one stone’. Prostaglandins Leukot Essent Fatty Acids 53:1–11

    PubMed  Google Scholar 

  • Di Marzo V, Matias I (2005) Endocannabinoid control of food intake and energy balance. Nat Neurosci 8:585–589

    PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Sugiura T, Waku K (1996) Potential biosynthetic connections between the two cannabimimetic eicosanoids, anandamide and 2-arachidonoyl-glycerol, in mouse neuroblastoma cells. Biochem Biophys Res Commun 227:281–288

    PubMed  Google Scholar 

  • Di Marzo V, Bisogno T, Sugiura T, Melck D, De Petrocellis L (1998) The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by neuronal- and basophil-like cells: connections with anandamide. Biochem J 331:15–19

    PubMed  Google Scholar 

  • Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G (1999a) Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. Eur J Biochem 264:258–267

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Bisogno T, Melck D (1999b) Metabolism of anandamide and 2-arachidonoylglycerol: an historical overview and some recent developments. Lipids 34:319–325

    Google Scholar 

  • Di Marzo V, Hill MP, Bisogno T, Crossman AR, Brotchie JM (2000) Enhanced levels of endogenous cannabinoids in the globus pallidus are associated with a reduction in movement in an animal model of Parkinson's disease. FASEB J 14:1432–1438

    PubMed  Google Scholar 

  • Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410:822–825

    PubMed  Google Scholar 

  • Di Marzo V, De Petrocellis L, Fezza F, Ligresti A, Bisogno T (2002) Anandamide receptors. Prostaglandins Leukot Essent Fatty Acids 66:377–391

    PubMed  Google Scholar 

  • Di Marzo V, van der Stelt M, Mazzola C, et al (2005) Dual effect of inhibitors of endocannabinoid inactivation on memory retention in experimental models of Alzheimer's disease. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24–27 June 2005. International Cannabinoid Research Society, Burlington, p 75

    Google Scholar 

  • Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (2002a) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824

    PubMed  CAS  Google Scholar 

  • Dinh TP, Freund TF, Piomelli D (2002b) A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids 121:149–158

    PubMed  CAS  Google Scholar 

  • Dinh TP, Kathuria S, Piomelli D (2004) RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol. Mol Pharmacol 66:1260–1264

    PubMed  CAS  Google Scholar 

  • Egertova M, Cravatt BF, Elphick MR (2003) Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Neuroscience 119:481–496

    PubMed  CAS  Google Scholar 

  • Fattore L, Spano MS, Cossu G, Deiana S, Fratta W (2003) Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats. Eur J Neurosci 17:1723–1726

    PubMed  CAS  Google Scholar 

  • Fegley D, Kathuria S, Mercier R, Li C, Goutopoulos A, Makriyannis A, Piomelli D (2004) Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA 101:8756–8761

    PubMed  CAS  Google Scholar 

  • Fegley D, Gaetani S, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide and oleoylethanolamide deactivation. J Pharmacol Exp Ther 313:352–358

    PubMed  CAS  Google Scholar 

  • Fernandez-Espejo E, Caraballo I, de Fonseca FR, El Banoua F, Ferrer B, Flores JA, Galan-Rodriguez B (2005) Cannabinoid CB1 antagonists possess antiparkinsonian efficacy only in rats with very severe nigral lesion in experimental parkinsonism. Neurobiol Dis 18:591–601

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Fowler CJ, Jonsson KO, Tiger G (2001) Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 2001 62:517–526

    CAS  Google Scholar 

  • 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

    Google Scholar 

  • Ghafouri N, Tiger G, Razdan RK, Mahadevan A, Pertwee RG, Martin BR, Fowler CJ (2004) Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol. Br J Pharmacol 143:774–784

    PubMed  CAS  Google Scholar 

  • Glass M, Hong J, Sato TA, Mitchell MD (2005) Misidentification of prostamides as prostaglandins. J Lipid Res 46:1364–1368

    PubMed  CAS  Google Scholar 

  • Goparaju SK, Ueda N, Yamaguchi H, Yamamoto S (1998) Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand. FEBS Lett 422:69–73

    PubMed  CAS  Google Scholar 

  • Goparaju SK, Ueda N, Taniguchi K, Yamamoto S (1999) Enzymes of porcine brain hydrolyzing 2-arachidonoylglycerol, an endogenous ligand of cannabinoid receptors. Biochem Pharmacol 57:417–423

    PubMed  CAS  Google Scholar 

  • Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F, Freund TF (2004) Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20:441–458

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Hajos N, Kathuria S, Dinh T, Piomelli D, Freund TF (2004) Endocannabinoid transport tightly controls 2-arachidonoyl glycerol actions in the hippocampus: effects of low temperature and the transport inhibitor AM404. Eur J Neurosci 19:2991–2996

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Hashimotodani Y, Ohno-Shosaku T, Tsubokawa H, Ogata H, Emoto K, Maejima T, Araishi K, Shin HS, Kano M (2005) Phospholipase Cbeta serves as a coincidence detector through its Ca2+ dependency for triggering retrograde endocannabinoid signal. Neuron 45:257–268

    PubMed  CAS  Google Scholar 

  • Hillard CJ, Jarrahian A (2003) Cellular accumulation of anandamide: consensus and controversy. Br J Pharmacol 140:802–808

    PubMed  CAS  Google Scholar 

  • Ho SY, Delgado L, Storch J (2002) Monoacylglycerol metabolism in human intestinal Caco-2 cells: evidence for metabolic compartmentation and hydrolysis. J Biol Chem 277:1816–1823

    PubMed  CAS  Google Scholar 

  • Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 247 Suppl 1:345–358

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Jarai Z, Wagner JA, Goparaju SK, Wang L, Razdan RK, Sugiura T, Zimmer AM, Bonner TI, Zimmer A, Kunos G (2000) Cardiovascular effects of 2-arachidonoyl glycerol in anesthetized mice. Hypertension 35:679–684

    PubMed  CAS  Google Scholar 

  • Karlsson M, Contreras JA, Hellman U, Tornqvist H, Holm C (1997) cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J Biol Chem 272:27218–27223

    PubMed  CAS  Google Scholar 

  • Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, Giustino A, Tattoli M, Palmery M, Cuomo V, Piomelli D (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9:76–81

    PubMed  CAS  Google Scholar 

  • Kim J, Alger BE (2004) Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus. Nat Neurosci 7:697–698

    PubMed  CAS  Google Scholar 

  • Koda N, Tsutsui Y, Niwa H, Ito S, Woodward DF, Watanabe K (2004) Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and identification of Bimatoprost as a potent inhibitor of the enzyme: new enzyme assay method using LC/ESI/MS. Arch Biochem Biophys 424:128–136

    PubMed  CAS  Google Scholar 

  • Kojima S, Sugiura T, Waku K, Kamikawa Y (2002) Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of longitudinal smooth muscle from the guinea-pig distal colon in vitro. Eur J Pharmacol 444:203–207

    PubMed  CAS  Google Scholar 

  • Kondo S, Kondo H, Nakane S, Kodaka T, Tokumura A, Waku K, Sugiura T (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 Lett 429:152–156

    PubMed  CAS  Google Scholar 

  • Kozak KR, Marnett LJ (2002) Oxidative metabolism of endocannabinoids. Prostaglandins Leukot Essent Fatty Acids 66:211–220

    PubMed  CAS  Google Scholar 

  • Kozak KR, Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R, Jakobsson PJ, Marnett LJ (2002a) Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 277:44877–44885

    PubMed  CAS  Google Scholar 

  • Kozak KR, Gupta RA, Moody JS, Ji C, Boeglin WE, DuBois RN, Brash AR, Marnett LJ (2002b) 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome proliferator-activated receptor alpha agonist. J Biol Chem 277:23278–23286

    PubMed  CAS  Google Scholar 

  • Kozak KR, Prusakiewicz JJ, Rowlinson SW, Prudhomme DR, Marnett LJ (2003) Amino acid determinants in cyclooxygenase-2 oxygenation of the endocannabinoid anandamide. Biochemistry 42:9041–9049

    PubMed  CAS  Google Scholar 

  • Kurahashi Y, Ueda N, Suzuki H, Suzuki M, Yamamoto S (1997) Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase. Biochem Biophys Res Commun 237:512–515

    PubMed  CAS  Google Scholar 

  • Lichtman AH, Hawkins EG, Griffin G, Cravatt BF (2002) Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. J Pharmacol Exp Ther 302:73–79

    PubMed  CAS  Google Scholar 

  • Lichtman AH, Leung D, Shelton CC, Saghatelian A, Hardouin C, Boger DL, Cravatt BF (2004) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther 311:441–448

    PubMed  CAS  Google Scholar 

  • Ligresti A, Morera E, Van Der Stelt M, Monory K, Lutz B, Ortar G, Di Marzo V (2004) Further evidence for the existence of a specific process for the membrane transport of anandamide. Biochem J 380:265–272

    PubMed  CAS  Google Scholar 

  • 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-kappaB independently of platelet-activating factor. J Biol Chem 278:45034–45039

    PubMed  CAS  Google Scholar 

  • Liu J, Harvey-White J, Kunos G (2005) Novel anandamide biosynthetic pathway in RAW264.7 macrophages. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24–27 June 2005. International Cannabinoid Research Society, Burlington, p 119

    Google Scholar 

  • Maccarrone M, Bari M, Lorenzon T, Bisogno T, Di Marzo V, Finazzi-Agro A (2000a) Anandamide uptake by human endothelial cells and its regulation by nitric oxide. J Biol Chem 275:13484–13492

    PubMed  CAS  Google Scholar 

  • Maccarrone M, De Felici M, Bari M, Klinger F, Siracusa G, Finazzi-Agro A (2000b) Down-regulation of anandamide hydrolase in mouse uterus by sex hormones. Eur J Biochem 267:2991–2997

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Bisogno T, Valensise H, Lazzarin N, Fezza F, Manna C, Di Marzo V, Finazzi-Agro A (2002) Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. Mol Hum Reprod 8:188–195

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Bari M, Di Rienzo M, Finazzi-Agro A, Rossi A (2003a) Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin. J Biol Chem 278:32726–32732

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Di Rienzo M, Finazzi-Agro A, Rossi A (2003b) Leptin activates the anandamide hydrolase promoter in human T lymphocytes through STAT3. J Biol Chem 278:13318–13324

    PubMed  CAS  Google Scholar 

  • Maccarrone M, Fride E, Bisogno T, Bari M, Cascio MG, Battista N, Finazzi Agro A, Suris R, Mechoulam R, Di Marzo V (2005) Up-regulation of the endocannabinoid system in the uterus of leptin knockout (ob/ob) mice and implications for fertility. Mol Hum Reprod 11:21–28

    PubMed  CAS  Google Scholar 

  • Markey SP, Dudding T, Wang TC (2000) Base- and acid-catalyzed interconversions of O-acyl- and N-acyl-ethanolamines: a cautionary note for lipid analyses. J Lipid Res 41:657–662

    PubMed  CAS  Google Scholar 

  • Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schutz G, Zieglgansberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88

    PubMed  CAS  Google Scholar 

  • Matias I, Chen J, De Petrocellis L, Bisogno T, Ligresti A, Fezza F, Krauss AH, Shi L, Protzman CE, Li C, Liang Y, Nieves AL, Kedzie KM, Burk RM, Di Marzo V, Woodward DF (2004) Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism. J Pharmacol Exp Ther 309:745–757

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Mazzola C, Micale V, Drago F (2003) Amnesia induced by beta-amyloid fragments is counteracted by cannabinoid CB1 receptor blockade. Eur J Pharmacol 477:219–225

    PubMed  CAS  Google Scholar 

  • McAllister SD, Glass M (2002) CB(1) and CB(2) receptor-mediated signalling: a focus on endocannabinoids. Prostaglandins Leukot Essent Fatty Acids 66:161–171

    PubMed  CAS  Google Scholar 

  • McFarland MJ, Barker EL (2004) Anandamide transport. Pharmacol Ther 104:117–135

    PubMed  CAS  Google Scholar 

  • McHugh D, McMaster RS, Pertwee RG, Roy S, Mahadevan A, Razdan R, Ross RA (2006) Novel compounds that interact with both leukotiene BLT and vanilloid TRPV1 receptors. J Pharmacol Exp Ther 316(2):955–965

    PubMed  CAS  Google Scholar 

  • McKinney MK, Cravatt BF (2005) Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 74:411–432

    PubMed  CAS  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

    PubMed  CAS  Google Scholar 

  • Melis M, Perra S, Muntoni AL, Pillolla G, Lutz B, Marsicano G, Di Marzo V, Gessa GL, Pistis M (2004a) Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons. J Neurosci 24:10707–10715

    PubMed  CAS  Google Scholar 

  • Melis MR, Succu S, Mascia MS, Argiolas A (2004b) Antagonism of cannabinoid CB1 receptors in the paraventricular nucleus of male rats induces penile erection. Neurosci Lett 359:17–20

    PubMed  CAS  Google Scholar 

  • Mestre L, Correa F, Arevalo-Martin A, Molina-Holgado E, Valenti M, Ortar G, Di Marzo V, Guaza C (2005) Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J Neurochem 92:1327–1339

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Natarajan V, Schmid PC, Schmid HH (1986) N-acylethanolamine phospholipid metabolism in normal and ischemic rat brain. Biochim Biophys Acta 878:32–41

    PubMed  CAS  Google Scholar 

  • Nirodi CS, Crews BC, Kozak KR, Morrow JD, Marnett LJ (2004) The glyceryl ester of prostaglandin E2 mobilizes calcium and activates signal transduction in RAW264.7 cells. Proc Natl Acad Sci USA 101:1840–1845

    PubMed  CAS  Google Scholar 

  • Nithipatikom K, Endsley MP, Isbell MA, Wheelock CE, Hammock BD, Campbell WB (2005) A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells. Biochem Biophys Res Commun 332:1028–1033

    PubMed  CAS  Google Scholar 

  • Oddi S, Bari M, Battista N, Barsacchi D, Cozzani I, Maccarrone M (2005) Confocal microscopy and biochemical analysis reveal spatial and functional separation between anandamide uptake and hydrolysis in human keratinocytes. Cell Mol Life Sci 62:386–395

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Ortar G, Ligresti A, De Petrocellis L, Morera E, Di Marzo V (2003) Novel selective and metabolically stable inhibitors of anandamide cellular uptake. Biochem Pharmacol 65:1473–1481

    PubMed  CAS  Google Scholar 

  • Ortega-Gutierrez S, Hawkins EG, Viso A, Lopez-Rodriguez ML, Cravatt BF (2004) Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake. Biochemistry 43:8184–8190

    PubMed  CAS  Google Scholar 

  • Petersen G, Hansen HS (1999) N-acylphosphatidylethanolamine-hydrolysing phospholipase D lacks the ability to transphosphatidylate. FEBS Lett 455:41–44

    PubMed  CAS  Google Scholar 

  • Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301:1020–1024

    PubMed  CAS  Google Scholar 

  • Ronesi J, Gerdeman GL, Lovinger DM (2004) Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport. J Neurosci 24:1673–1679

    PubMed  CAS  Google Scholar 

  • Ross RA, Craib SJ, Stevenson LA, Pertwee RG, Henderson A, Toole J, Ellington HC (2002) Pharmacological characterization of the anandamide cyclooxygenase metabolite: prostaglandin E2 ethanolamide. J Pharmacol Exp Ther 301:900–907

    PubMed  CAS  Google Scholar 

  • Saario SM, Savinainen JR, Laitinen JT, Jarvinen T, Niemi R (2004) Monoglyceride lipase-like enzymatic activity is responsible for hydrolysis of 2-arachidonoylglycerol in rat cerebellar membranes. Biochem Pharmacol 67:1381–1387

    PubMed  CAS  Google Scholar 

  • Saario SM, Salo OM, Nevalainen T, Poso A, Laitinen JT, Jarvinen T, Niemi R (2005) Characterization of the sulfhydryl-sensitive site in the enzyme responsible for hydrolysis of 2-arachidonoyl-glycerol in rat cerebellar membranes. Chem Biol 12:649–656

    PubMed  CAS  Google Scholar 

  • Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF (2004) Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry 43:14332–14339

    PubMed  CAS  Google Scholar 

  • Schmid HH, Schmid PC, Natarajan V (1990) N-Acylated glycerophospholipids and their derivatives. Prog Lipid Res 29:1–43

    PubMed  CAS  Google Scholar 

  • Schmid HH, Schmid PC, Natarajan V (1996) The N-acylation-phosphodiesterase pathway and cell signalling. Chem Phys Lipids 80:133–142

    PubMed  CAS  Google Scholar 

  • Slanina KA, Schweitzer P (2005) Inhibition of cyclooxygenase-2 elicits a CB1-mediated decrease of excitatory transmission in rat CA1 hippocampus. Neuropharmacology 49:653–659

    PubMed  CAS  Google Scholar 

  • Soria G, Mendizabal V, Tourino C, Robledo P, Ledent C, Parmentier M, Maldonado R, Valverde O (2005) Lack of CB1 cannabinoid receptor impairs cocaine self-administration. Neuropsychopharmacology 30:1670–1680

    PubMed  CAS  Google Scholar 

  • Steffens M, Schulze-Bonhage A, Surges R, Feuerstein TJ (2005) Fatty acid amidohydrolase in human neocortex-activity in epileptic and non-epileptic brain tissue and inhibition by putative endocannabinoids. Neurosci Lett 385:13–17

    PubMed  CAS  Google Scholar 

  • Stella N, Schweitzer P, Piomelli D (1997) A second endogenous cannabinoid that modulates long-term potentiation. Nature 388:773–778

    PubMed  CAS  Google Scholar 

  • Sugiura T, Waku K (2002) Cannabinoid receptors and their endogenous ligands. J Biochem (Tokyo) 132:7–12

    CAS  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku KR (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97

    PubMed  CAS  Google Scholar 

  • Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Waku K (1996) Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca(2+)-dependent transacylase and phosphodiesterase activities. Biochem Biophys Res Commun 218:113–117

    PubMed  CAS  Google Scholar 

  • Sugiura T, Kobayashi Y, Oka S, Waku K (2002) Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 66:173–192

    PubMed  CAS  Google Scholar 

  • Sun YX, Tsuboi K, Okamoto Y, Tonai T, Murakami M, Kudo I, Ueda N (2004) Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D. Biochem J 380:749–756

    PubMed  CAS  Google Scholar 

  • Tsuboi K, Sun YX, Okamoto Y, Araki N, Tonai T, Ueda N (2005) Molecular characterization of N-acylethanolamine-hydrolyzing acid amidase, a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase. J Biol Chem 280:11082–11092

    PubMed  CAS  Google Scholar 

  • Ueda N (2002) Endocannabinoid hydrolases. Prostaglandins Other Lipid Mediat 68–69:521–534

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Valenti M, Vigano D, Casico MG, Rubino T, Steardo L, Parolaro D, Di Marzo V (2004) Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain. Cell Mol Life Sci 61:945–950

    PubMed  CAS  Google Scholar 

  • van der Stelt M, Di Marzo V (2004) Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels. Eur J Biochem 271:1827–1834

    Google Scholar 

  • van der Stelt M, van Kuik JA, Bari M, van Zadelhoff G, Leeflang BR, Veldink GA, Finazzi-Agro A, Vliegenthart JF, Maccarrone M (2002) Oxygenated metabolites of anandamide and 2-arachidonoylglycerol: conformational analysis and interaction with cannabinoid receptors, membrane transporter, and fatty acid amide hydrolase. J Med Chem 45:3709–3720

    PubMed  Google Scholar 

  • van der Stelt M, Fox SH, Hill M, Crossman AR, Petrosino S, Di Marzo V, Brotchie JM (2005) A role for endocannabinoids in the generation of parkinsonism and levodopa-induced dyskinesia in MPTP-lesioned non-human primate models of Parkinson's disease. FASEB J 19:1140–1142

    PubMed  Google Scholar 

  • Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S; RIO-Europe Study Group (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365:1389–1397

    PubMed  Google Scholar 

  • Watanabe S, Doshi M, Hamazaki T (2003) n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice. Prostaglandins Leukot Essent Fatty Acids 69:51–59

    PubMed  CAS  Google Scholar 

  • Weber A, Ni J, Ling KH, Acheampong A, Tang-Liu DD, Burk R, Cravatt BF, Woodward D (2004) Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry. J Lipid Res 45:757–763

    PubMed  CAS  Google Scholar 

  • Williams EJ, Walsh FS, Doherty P (2003) The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response. J Cell Biol 160:481–486

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, Andrews SW, Shi L, Liang Y, Kedzie KM, Chen R, Gil DW, Kharlamb A, Archeampong A, Ling J, Madhu C, Ni J, Rix P, Usansky J, Usansky H, Weber A, Welty D, Yang W, Tang-Liu DD, Garst ME, Brar B, Wheeler LA, Kaplan LJ (2001) The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol 4:S337–S345

    Google Scholar 

  • Woodward DF, Krauss AH, Chen J, Liang Y, Li C, Protzman CE, Bogardus A, Chen R, Kedzie KM, Krauss HA, Gil DW, Kharlamb A, Wheeler LA, Babusis D, Welty D, Tang-Liu DD, Cherukury M, Andrews SW, Burk RM, Garst ME (2003) Pharmacological characterization of a novel antiglaucoma agent, Bimatoprost (AGN 192024). J Pharmacol Exp Ther 305:772–785

    PubMed  CAS  Google Scholar 

  • Woodward DF, Krauss AH-P, Nieves AL, et al (2005) First report of a prostaglandin ethanolamide (prostamide) receptor antagonist AGN 20439. XV Conference of the International Cannabinoid Research Society, Clearwater Beach, 24–27 June 2005. International Cannabinoid Research Society, Burlington, p 70

    Google Scholar 

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Acknowledgements

I am grateful to Dr. Stefania Petrosino for her help during the preparation of this manuscript.

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  1. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Comprensorio Olivetti, Fabbr. 70, 80078, Pozzuoli (NA), Italy

    V. Di Marzo

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S.G. Amara E. Bamberg B. Fleischmann T. Gudermann S.C. Hebert R. Jahn W.J. Lederer R. Lill A. Miyajima S. Offermanns R. Zechner

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Di Marzo, V. (2006). Endocannabinoids: synthesis and degradation. In: Amara, S., et al. Reviews of Physiology Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/112_0505

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