Chapter 9 The Endocannabinoid Anandamide. From Immunomodulation to Neuroprotection. Implications for Multiple Sclerosis

Vitamins and Hormones

Volumn 81, Issue C, 2009, Pages 207-230

  Correa, Fernando G ^a   Mestre, Leyre ^a   Docagne, Fabián ^a   Borrell, José ^a   Guaza, Carmen ^a  

^a INSTITUTO CAJAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; ANANDAMIDE; ARACHIDONIC ACID DERIVATIVE; CYTOKINE; ENDOCANNABINOID; IMMUNOLOGIC FACTOR; INTERLEUKIN 12; NEUROPROTECTIVE AGENT;

ANIMAL; GLIA; HUMAN; MULTIPLE SCLEROSIS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ARACHIDONIC ACIDS; CYTOKINES; ENDOCANNABINOIDS; HUMANS; IMMUNOLOGIC FACTORS; INTERLEUKIN-12; MULTIPLE SCLEROSIS; NEUROGLIA; NEUROPROTECTIVE AGENTS; POLYUNSATURATED ALKAMIDES; SIGNAL TRANSDUCTION;

EID: 67651171245     PISSN: 00836729     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0083-6729(09)81009-1     Document Type: Review

References (110)

1. 2 receptor mediates immunoglobulin switching from IgM to IgE in cultures of murine purified B lymphocytes. J. Neuroimmune Pharmacol. 3 1 (2008) 35-42
2. Arévalo-Martín A., Vela J.M., Molina-Holgado E., Borrell J., and Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J. Neurosci. 23 (2003) 2511-2516
3. 2 cannabinoid receptors as an emerging target for demyelinating diseases: From neuroimmune interactions to cell replacement strategies. Br. J. Pharmacol. 153 (2008) 216-225
4. Baker D., Pryce G., Croxford J.L., Brown P., Pertwee R.G., Makriyannis A., Khanolkar A., Layward L., Fezza F., Bisogno T., and Di Marzo V. Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J. 15 (2001) 300-302
5. Benito C., Nuñez E., Tolón R.M., Carrier E.J., Rábano A., Hillard C.J., and Romero J. Cannabinoid CB2 receptors and fatty cid amide hydrolase are selectively overexpressed in neuritis plaques-associated glia in Alzheimer disease. J. Neurosci. 23 (2003) 11136-11141
6. 2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J. Neurosci. 27 (2007) 2396-2402
7. Breivogel C.S., Griffin G., Di Marzo V., and Martin B.R. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol. Pharmacol. 60 (2001) 155-163
8. Cabral G.A., and Marciano-Cabral F. Cannabinoid receptors in microglia of the central nervous system: Immune functional relevance. J. Leukoc. Biol. 78 (2005) 1192-1197
9. Cabranes A., Venderoka K., de Lago E., Fezza F., Sanchez A., Mestre L., Valenti M., García-Merino A., Ramos J.A., Di Marzo V., and Fernandez-Ruiz J. Decreased endocannabinoid levels in the brain and beneficial effects of agents activating cannabinoid and/or vanilloid receptors in a rat model of multiple sclerosis. Neurobiol. Dis. 20 (2005) 207-217
10. 2 receptors during B-cell differentiation. Blood 92 (1998) 3605-3615
11. 2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int. Immunopharmacol 2 (2002) 69-82
12. 2 receptor-dependent mechanism. Mol. Pharmacol. 65 (2004) 999-1007
13. Centonze D., Bari M., Rossi S., Prosperetti C., Furlan R., Fezza F., De Chiara V., Battistini L., Bernardi G., Bernardini S., Martino G., and Maccarrone M. The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain 130 10 (2007) 2543-2553
14. Centonze D., Battistinni L., and Maccarrone M. The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases. Curr. Pharm. Des. 14 23 (2008) 2370-2420
15. Correa F., Docagne F., Clemente D., Mestre L., Becker C., and Guaza C. Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: Possible involvement of the COX-2 metabolite prostamide E(2). Biochem. J. 409 (2008) 761-770
16. Correa F., Docagne F., Mestre L., Clemente D., Hernangómez M., Loría F., and Guaza C. A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem. Pharmacol. 77 (2009) 86-100 doi:10.1016/j.bcp.2008.09.014
17. Cravatt B.J., Demarest K., Patricelli M., Bracey M.H., Giang D.K., Martin B.R., and Lichtman A.H. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc. Natl. Acad. Sci. USA 98 (2001) 9371-9376
18. Croxford J.L., and Miller S.D. Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212-2. J. Clin. Invest. 111 (2003) 1231-1240
19. 2 in the promyelocytic cells HL-60. J. Biol. Chem. 275 (2000) 15621-15628
20. Devane W.A., Dysarz F.A., Johnson M.R., Melvin L.S., and Howlett A.C. Determination and characterization of a cannabinoid receptor in a rat brain. Mol. Pharmacol. 34 (1988) 605-613
21. Devane W.A., Hanus L., Breuer A., Pertwee R.G., Stevenson L.A., Griffin G., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 (1992) 1946-1949
22. Di Marzo V., Breivogel C.S., Tao Q., Bridgen D.T., Razdan R.K., Zimmer A.M., Zimmer A., and Martin B.R. Levels, Metabolism, and pharmacological activity of anandamide in CB(1) cannabinoid receptor knockout mice: Evidence for non-CB(1), non-CB(2) receptor-mediated actions of anandamide in mouse brain. J. Neurochem. 75 (2000) 2434-2444
23. Di Marzo V., Fontana A., Cadas H., Schinelli S., Cimino G., Schwartz J.C., and Piomelli D. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372 (1994) 686-691
24. Di Marzo V., De Petrocellis L., Sepe N., and Buono A. Biosynthesis of anandamide and other acylethanolamides in mouse J744 macrophages and N18 neuroblastoma cells. Biochem. J. 316 3 (1996) 977-984
25. 2 receptors activation. Mol. Cell. Neurosci. 34 4 (2007) 551-561
26. 2 targeting in multiple sclerosis. Expert Opin. Ther. Targets 12 (2008) 185-195
27. 2 receptors. J. Neuroimmunol. 189 1-2 (2007) 17-22
28. Eljaschewitsch E., Witting A., Mawrin C., Lee T., Schmidt P.M., Wolf S., Hoertnalg H., Raine S.C., Scheneider-Stock R., Nitsch R., and Ulrich O. The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron 49 (2006) 67-79
29. Fachinetti F., Del Giudice G., Furegato S., Passarotto M., and Leon M. Cannabinoids ablate release of TNF alpha in rat microglial cells stimulated with lypopolysaccharide. Glia 41 (2003) 161-168
30. Felder C.C., Briley E.M., Axelrod J., Simpson J.T., Mackie K., and Devane W.A. Anandamide, an endogenous cannabimimetic eicosanoid. Binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc. Natl. Acad. Sci. USA 90 (1993) 7656-7660
31. 2 receptors in neuroprotective effects of cannabinoids. Mol. Cell. Endocrinol. 286 (2008) 91-96
32. Fowler C.J. The contribution of cyclooxygenase-2 to endocannabinoid metabolism and action. Br. J. Pharmacol. 152 5 (2007) 744-750
33. Galiègue S., Mary S., Marchand J., Dussossoy D., Carrière D., Carayon P., Bouaboula M., Shire D., Le Fur G., and Casellas P. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem. 232 (1995) 54-61
34. Gaoni Y., and Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 86 (1964) 1646-1647
35. García-Ovejero D., Arévalo-Martin A., Petrosino S., Docagne F., Hagen C., Bisogno T., Watanabe M., Guaza C., Di Marzo V., and Molina-Holgado E. The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol. Dis. 33 (2009) 57-71
36. 2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes. Mol. Immunol. 43 (2006) 2169-2179
37. Giufrida A., Parsons L.H., Kerr T.M., Rodriguez de Fonseca F., Navarro M., and Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat. Neurosci. 2 (1999) 358-363
38. Hanisch U.K., and Kettenmann H. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10 11 (2007) 1387-1394
39. Howlett A.C., Barth F., Bonner T.I., Cabral G., Casellas P., Devane W.A., Felder C.C., Herhkenman M., Mackie K., Martin B.R., Mechoulam R., and Pertwee R.G. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 54 (2002) 161-202
40. Howlett A.C. Cannabinoid receptor signalling. Handb. Exp. Pharmacol. 168 (2005) 53-79
41. 2 receptors. Proc. Natl. Acad. Sci. USA 23 24 (1999) 14136-14141
42. Kaplan B.L., Rockwell C.E., and Kaminski N.E. Evidence for cannabinoid dependent and independent mechanisms of actions on leukocytes. J. Pharmacol. Exp. Ther. 306 3 (2003) 1077-1085
43. Khaspekov L.G., Brenz M.S., Frumkina L.E., Hermann H., Marsicano G., and Lutz B. Involvement of brain-derived neurotrophic factor in cannabinoid-dependent protection against excitotoxicity. Eur. J. Neurosci. 19 (2004) 1691-1698
44. Klein T.W. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 5 (2005) 400-411
45. Klein T.W., and Newton C.A. Therapeutic potential of cannabinoid-based drugs. Adv. Exp. Med. Biol. 601 (2007) 395-413
46. Klein T.W., Newton C., Larsen K., Chou J., Perkins I., Lu L., Nong L., and Friedman H. Cannabinoid receptors and T helper cells. J. Neuroimmunol. 147 (2004) 91-94
47. Lambert D.M., and Fowler C.J. The endocannabinoid system: Drug targets, lead compounds and potential therapeutic applications. J. Med. Chem. 48 (2005) 5059-5087
48. Li J., Gran B., Zhang G.X., Ventura E.S., Siglienti I., Rostami A., and Kamoun M. Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J. Neurol. Sci. 215 (2003) 95-103
49. Ligresti A., Cascio M.G., Pryce G., Kulasegram S., Beletskaya I., De Petrocellis L., Saha B., Mahadevan A., Visintin C., Wiley J.L., Baker D., Martin B.R., et al. New potent and selective inhibitors of anandamide reuptake with antispastic activity in a mouse model of multiple sclerosis. Br. J. Pharmacol. 147 (2006) 83-91
50. Liu J., Batkai S., Pacher P., Harvey-White J., Wagner J.A., Cravatt B.J., Gao B., and Kunos G. Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-kappaB independently of platelet-activating factor. J. Biol. Chem. 278 (2003) 45034-45039
51. Liu J., Wang L., Harvey-White J., Osei-Hyiaman D., Razdan R., Gong Q., Chan A.C., Zhou Z., Huang B.X., Kim H.Y., and Kunos G. A biosynthetic pathway for anandamide. Proc. Natl. Acad. Sci. USA 103 (2006) 13345-13350
52. López-Rodríguez M.L., Viso A., Ortega-Gutiérrez S., Fowler C.J., Tiger G., de Lago E., Fernández-Ruiz J., and Ramos J.A. Design, synthesis, and biological evaluation of new inhibitors of the endocannabinoid uptake: Comparison with effects on fatty acid amidohydrolase. J. Med. Chem. 46 (2003) 1512-1522
53. Loría F., Petrosino S., Mestre L., Spagnolo A., Correa F., Hernangómez M., Di Marzo V., Guaza C., and Docagne F. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur. J. Neurosci. 28 (2008) 633-641
54. Maresz K., Carrier E.J., Ponomarev E.D., Hillard C.J., and Dittel B.N. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J. Neurochem. 95 (2005) 437-445
55. Maresz K., Pryce G., Ponomarev E.D., Marsicano G., Croxford J.L., Shriver L.P., Ledent C., Cheng X., Carrier E.J., Mann M.K., Giovannoni G., Pertwee R.G., et al. Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat. Med. 13 (2007) 492-497
56. 1 cannabinoid receptors on-demand defense against excitotoxicity. Science 302 (2003) 84-88
57. Matias I., Pochard P., Orlando P., Salzet M., Pestel J., and Di Marzo V. Presence and regulation of the endocannabinoid system in human dendritic cells. Eur. J. Biochem. 269 (2002) 3771-3778
58. Matias I., Chen J., De Petrocellis L., Bisogno T., Ligresti A., Fezza F., Krauss A.H., Shi L., Protzman C.E., Li C., Liang Y., Nieves A.L., et al. Prostaglandin ethanolamides (prostamides): In vitro pharmacology and metabolism. J. Pharmacol. Exp. Ther. 309 (2004) 745-757
59. Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., and Bonner T.I. Structure of a cannabinoid and functional expression of the cloned cDNA. Nature 346 (1990) 561-564
60. Mc Coy K.L., Matmeyeva M., Carlisle S.J., and Cabral G.A. Cannabinoid inhibition of the processing of intact lysozyme by macrophages: Evidence for CB2 receptor participation. J. Pharmacol. Exp. Ther. 289 (1999) 1620-1625
61. McHugh D., Tanner C., Mechoulam R., Pertwee R.G., and Ross R.A. Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: Evidence for a site distinct of CB1 and CB2. Mol. Pharmacol. 73 2 (2008) 441-450
62. Mechoulam R., Ben-Shabat S., Hanus L., Ligumsky M., Kaminski N.E., Schatz A.R., Gopher A., Almog S., Martin B.R., Compton D.R., Pertwee R.G., Griffin G., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50 (1995) 83-90
63. Mestre L., Correa F., Arévalo-Martín A., Molina-Holgado E., Valenti M., Ortar G., Di Marzo V., and Guaza C. Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J. Neurochem. 92 (2005) 1327-1339
64. 2 release in murine brain derived endothelial cells following Theiler's virus infection. Biochem. Pharmacol. 72 (2006) 869-880
65. Mestre L., Docagne F., Correa F., Loría F., Hernangómez M., Borrell J., and Guaza C. A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules. Mol. Cell Neurosci. 40 (2009) 258-266
66. Molina-Holgado F., Lledó A., and Guaza C. Anandamide suppresses nitric oxide and TNF-α responses to Theiler's virus or endotoxin in astrocytes. Neuroreport 8 (1997) 1929-1933
67. Molina-Holgado F., Molina-Holgado E., and Guaza C. The endogenous cannabinoid anandamide potentiates IL-6 production by astrocytes infected with Theiler's murine encephalomyelitis virus by a receptor-mediated pathway. FEBS Lett. 433 (1998) 139-142
68. Molina-Holgado F., Molina-Holgado E., Guaza C., and Rothwell N.J. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide induced nitric oxide release in astrocyte cultures. J. Neurosci. Res. 67 (2002) 829-836
69. Molina-Holgado E., Vela J.M., Arévalo-Martín A., Almazán G., Molina-Holgado F., Borrell J., and Guaza C. Cannabinoids promote oligodendrocyte progenitor survival: Involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J. Neurosci. 22 22 (2002) 9742-9753
70. Molina-Holgado F., Pinteaux E., Moore J., Molina-Holgado E., Guaza C., Gibson R.M., and Rothwell N. Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glial cells. J. Neurosci. 23 (2003) 6470-6474
71. Monory K., Blaudzum H., Massa F., Kaiser N., Lemberger T., Schtz G., Wotjak C.T., Luzt B., and Marsicano G. Genetic dissection of behavioural and autonomic effects of delta-9-tetrahydrocannabinol in mice. PLoS Biology (2007) e269
72. Muccioli G.G., Xu C., Odah E., Cudaback E., Cisneros J.A., Lambert D.M., López Rodríguez M.L., Bajjalieh S., and Stella N. Identification of a novel endocannabinoid-hydrolyzing enzyme expressed by microglial cells. J. Neurosci. 27 11 (2007) 2883-2890
73. Munro S., Thomas K.L., and Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365 (1993) 61-65
74. Nagayama T., Sinor A.D., Simon R.P., Chen J., Graham S.H., Jin K., and Greenberg D.A. Cannabinoids and neuroprotection in focal and global cerebral ischemia and neuronal cultures. J. Neurosci. 19 (1999) 2987-2995
75. Nakajima Y., Furuichim Y., Biswas K.K., Hashiguchi T., Kawahara K., Yamaji K., Uchimura T., Izumi Y., and Maruyama I. Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition. FEBS Lett. 580 (2006) 613-619
76. Offèrtaler L., Mo F.M., Batkai S., Liu J., Begg M., Razdan R.K., Martin B.R., Bukoski R.D., and Kunos G. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol. Pharmacol. 63 (2003) 699-705
77. Ortar G., Ligresti A., de Petrocellis L., Morera E., and Di Marzo V. Novel selective and metabolically stable inhibitors of anandamide cellular uptake. Biochem. Pharmacol. 65 (2003) 1475-1481
78. Ortega-Gutiérrez S., Molina-Holgado E., and Guaza C. Effect of anandamide uptake inhibition in the production of nitric oxide and in the release of cytokines in astrocyte cultures. Glia 52 (2005) 166-168
79. Ortega-Gutiérrez S., Molina-Holgado E., Arévalo-Martín A., Correa F., Viso A., López-Rodríguez M.L., Di Marzo V., and Guaza C. Activation of the endocannabinoid system as therapeutic approach in a murine model of multiple sclerosis. FASEB J. 19 (2005) 1338-1340
80. O'sullivan S.E. Cannabinoids go nuclear: Evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol. 152 5 (2007) 576-582
81. 2 cannabinoid receptor controls myeloid progenitor trafficking. Involvement in the pathogenesis of an animal model of multiple sclerosis. J. Biol. Chem. 283 (2008) 13320-13329
82. Pitt D., Werner P., and Raine C.S. Glutamate excitoxicity in a model of multiple sclerosis. Nat. Med. 6 (2000) 67-70
83. Pryce G., Ahmed Z., Hankey D.J., Jackson S.J., Croxford J.L., Pocock J.M., Ledent C., Petzold A., Thompson A.J., Giovannoni G., Cuzner M.L., and Baker D. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126 (2003) 2191-2202
84. Puffenbarger R.A., Boothe A.C., and Cabral G.A. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia 29 (2000) 58-69
85. Raivich G. Like cops of the beat: The active role of resting microglia. Trends Neurosci. 28 (2005) 571-573
86. Ramirez B.G., Blazquez C., Gómez del Pulgar T., Guzman M., and De Ceballos M. Prevention of Alzheimer's disease pathology by cannabinoids: Neuroprotection mediated by blockade of microglial activation. J. Neurosci. 25 (2005) 1904-1913
87. Rockwell C.E., and Kaminski N.E. A cyclooxygenase metabolite of anandamide causes inhibition of interleukin-2 secretion in murine splenocytes. J. Pharmacol. Exp. Ther. 311 (2004) 683-690
88. 2 ethanolamide. J. Pharmacol. Exp. Ther. 301 (2002) 900-907
89. Sanchez Galve-Roperth I., Canova C., Brachet P., and Guzmán M. Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett. 436 (1998) 6-10
90. Sancho R., Calzado M.A., Di Marzo V., Appendino G., and Muñoz E. Anandamide inhibits nuclear factor-kappa B activation through a cannabinoid receptor-independent pathway. Mol. Pharmacol. 63 2 (2003) 429-438
91. Sharchielli P., Greco L., Floridi A., and Gallai V. Excitatory amino acids and multiple sclerosis: Evidence from cerebrospinal fluid. Arch. Neurol. 60 (2003) 1082-1088
92. Shouman B., Fontaine R., Baud O., Schwendimann L., Keller M., Sppedding M., Lelievre V., and Gressens P. Endocannabinoids potently protect the new born brain against AMPA-kaniate receptor-mediated excitotoxicity damage. Br. J. Pharmacol. 148 (2006) 442-451.
93. Smith S.R., Terminelli C., and Denhardt G. Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice. J. Pharmacol. Exp. Ther. 293 (2000) 136-150
94. Srinivasan R., Sailasuta N., Hurd R., Nelson S., and Pelleetier D. Evidence of elevated glutamate in multiple sclerosis using magnetic resonante spectroscopy at 3 T. Brain 128 (2005) 1016-1025
95. Stella N. Cannabinoid signalling in glial cells. Glia 48 (2004) 267-277
96. Stella N. Endocannabinoid signalling in microglial cells. Neuropharmacology 1 (2009) 244-253
97. Sugiura T., Kondo S., Sukagawa A., Nakane S., Shinoda A., Itoh K., Yamashita A., and Waku K. 2-Arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215 (1995) 89-97
98. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol. 3 2 (2003) 133-146
99. 1 receptors in the rat central nervous system. Neuroscience 83 (1998) 393-411
100. 2 receptors. Science 310 (2005) 329-332
101. Vogel Z., Barg J., Levy R., Saya D., Hedaman E., and Mechoulam R. Anandamide a brain endogenous compound interacts specifically with the cannabinoid receptors and inhibits adenylate cyclase. J. Neurochem. 61 (1993) 352-355
102. Waldeck-Weiermair M., Zoratti C., Osibow K., Balenga N., Goessnitzer E., Waldhoer M., Malli R., and Graier W.F. Integrin clustering enables anandamide-induced Ca2+ signalling in endothelial cells via GPR55 by protection against CB1-triggered repression. J. Cell Sci. 121 (2008) 1704-1717
103. Walter L., Franklin A., Witting A., Moller T., and Stella N. Astrocytes in culture produce anandamide and other acylethanolamides. J. Biol. Chem. 277 (2002) 20869-20876
104. Walter L., Franklin A., Witting A., Wade C., Xie Y., Kunos G., and Stella N. Non-psychotropic cannabinoid receptors regulate microglia cell migration. J. Neurosci. 23 (2003) 1398-1405
105. Webb M., Luo L., Ma J.Y., and Tham C.S. Genetic deletion of fatty acid amide hydrolase results in improved long-term outcome in chronic autoimmune encephalitis. Neurosci. Lett. 439 1 (2008) 106-110
106. Witting P., Chen L., Cudaback E., Straiker A., Walter R., Rickman B., Moller T., Brosnan C., and Stella N. Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc. Natl. Acad. Sci. USA 103 (2006) 6362-6367
107. Witting A., Walter R., Moller T., and Stella N. P2X7 receptors control 2-arachidonoyl production by microglial cells. Proc. Natl. Acad. Sci. USA 101 (2004) 3214-3219
108. Yiangou Y., Facer P., Durrenberger P., Chessell I.P., Naylor A., Bountra C., Banati R.R., and Anand P. COX-2, CB2, and P2X7-immunoreactivities are increased in activated microglia cells/macrophages of multiple sclerosis and amytrophic lateral sclerosis spinal cord. BMC Neurol. 6 (2006) 12-16
109. Yuan M., Kiertscher S.M., Cheng Q., Zoumalan R., Tashkin D.P., and Roth M.D. Delta 9 tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J. Neuroimmunol. 133 (2002) 124-131
110. Zygmunt P.M., Petersson J., Andersson D.A., Chuang H., Sorgard M., Di Marzo V., Julius D., and Hogestatt E.D. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400 (1999) 452-457