CB2 Cannabinoid Receptors: Molecular, Signaling, and Trafficking Properties

  • Paul L. Prather

Two G protein-coupled receptors, CB1 and CB2, have thus far been identified and are responsible for most of the effects produced by cannabinoids. Cannabinoids, such as Δ9-THC, produce psychoactive effects through activation of neuronal CB1 receptors, while CB2 receptors mediate the immune properties of this class of drugs. The molecular, signaling, and trafficking properties of CB2 receptors will be the focus of this review. The cloning of CB2 receptors will be described, along with evidence that individual cannabinoid ligands, differing subtly in structure, might bind to CB2 receptors in distinct fashions. In addition, potential mechanisms underlying the dramatic upregulation of CB2 receptors in response to inflammatory stimuli will be discussed. Next, the currently known signal transduction pathways associated with CB2 receptor activation will be detailed, from G protein coupling to regulation of intracellular effectors. Evidence for the ability of different CB2 receptor agonists to distinctly regulate multiple effectors, known as agonist-directed trafficking of response (ADTR), will also be presented. Furthermore, a potential relationship between CB2 receptor ADTR and immune cell function will be discussed. Lastly, two distinct aspects of CB2 receptor signaling will be described that may help to explain the well-documented interactions of cannabinoids with other receptor systems. It is hoped that this brief review will provide a basic understanding of CB2 receptor signaling necessary to appreciate the exciting future approaching for the development of potentially therapeutic selective CB2 receptor ligands.


Adenylyl Cyclase Noid Receptor Microglial Cell Migration Noladin Ether Puffer Fish Fugu Rubripes 
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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  1. Alves ID, Salamon Z, Varga E, Yamamura HI, Tollin G, Hruby VJ (2003) Direct observation of G protein binding to the human delta-opioid receptor using plasmon-waveguide resonance spectroscopy. J Biol Chem 278:48890–48897.CrossRefPubMedGoogle Scholar
  2. Bayewitch M, Avidor-Reiss T, Levy R, Barg J, Mechoulam R, Vogel Z (1995) The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling. FEBS Lett 375:143–147.CrossRefPubMedGoogle Scholar
  3. Becher B, Antel JP (1996) Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia 18:1–10.CrossRefPubMedGoogle Scholar
  4. Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, Romero J (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141.PubMedGoogle Scholar
  5. Berg KA, Maayani S, Goldfarb J, Scaramellini C, Leff P, Clarke WP (1998) Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol Pharm 54:94–104.Google Scholar
  6. Bonhaus DW, Chang LK, Kwan J, Martin GR (1998) Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. J Pharmacol Exp Ther 287:884–888.PubMedGoogle Scholar
  7. Borner C, Hollt V, Kraus J (2006) Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Mol Pharm 69:1486–1491.CrossRefGoogle Scholar
  8. Borner C, Hollt V, Sebald W, Kraus J (2007) Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. J Leukoc Biol 81:336–343.CrossRefPubMedGoogle Scholar
  9. Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, Le Fur G, Casellas P (1995) Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 312:637–641.PubMedGoogle Scholar
  10. Bouaboula M, Poinot-Chazel C, Marchand J, Canat X, Bourrie B, Rinaldi-Carmona M, Calandra B, Le Fur G, Casellas P (1996) Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression. Eur J Biochem 237:704–711.CrossRefPubMedGoogle Scholar
  11. Bouaboula M, Desnoyer N, Carayon P, Combes T, Casellas P (1999a) G protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: implication for intracellular signalization cross-regulation. Mol Pharm 55:473–480.Google Scholar
  12. Bouaboula M, Dussossoy D, Casellas P (1999b) Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528. Implications for receptor biological responses. J Biol Chem 274:20397–20405.CrossRefPubMedGoogle Scholar
  13. Brotchie JM (2003) CB1 cannabinoid receptor signalling in Parkinson’s disease. Curr Opin Pharmacol 3:54–61.CrossRefPubMedGoogle Scholar
  14. Brown SM, Wager-Miller J, Mackie K (2002) Cloning and molecular characterization of the rat CB2 cannabinoid receptor. Biochim Biophys Acta 1576:255–264.PubMedGoogle Scholar
  15. Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305.CrossRefPubMedGoogle Scholar
  16. 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 Pharm 65:999–1007.CrossRefGoogle Scholar
  17. Cichewicz DL (2004) Synergistic interactions between cannabinoid and opioid analgesics. Life Sci 74:1317–1324.CrossRefPubMedGoogle Scholar
  18. Conti S, Costa B, Colleoni M, Parolaro D, Giagnoni G (2002) Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. Br J Pharmacol 135:181–187.CrossRefPubMedGoogle Scholar
  19. Cravatt B, Lichtman A (2004) The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol 61:149–160.CrossRefPubMedGoogle Scholar
  20. Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharm 48:443–450.Google Scholar
  21. Felder CC, Joyce KE, Briley EM, Glass M, Mackie KP, Fahey KJ, Cullinan GJ, Hunden DC, Johnson DW, Chaney MO, Koppel GA, Brownstein M (1998) LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J Pharmacol Exp Ther 284:291–297.PubMedGoogle Scholar
  22. Figini M, Emanueli C, Bertrand C, Sicuteri R, Regoli D, Geppetti P (1997) Differential activation of the epithelial and smooth muscle NK1 receptors by synthetic tachykinin agonists in guinea-pig trachea. Br J Pharmacol 121:773–781.CrossRefPubMedGoogle Scholar
  23. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61.CrossRefPubMedGoogle Scholar
  24. Galve-Roperh I, Sanchez C, Cortes ML, del Pulgar TG, Izquierdo M, Guzman M (2000) Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med 6:313–319.CrossRefPubMedGoogle Scholar
  25. Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279:129–134.PubMedGoogle Scholar
  26. Glass M, Felder CC (1997) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor. J Neurosci 17:5327–5333.PubMedGoogle Scholar
  27. Gomez del Pulgar T, Velasco G, Sanchez C, Haro A, Guzman M (2002) De novo-synthesized ceramide is involved in cannabinoid-induced apoptosis. Biochem J 363:183–188.CrossRefPubMedGoogle Scholar
  28. Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR (2006) Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 1071:10–23.CrossRefPubMedGoogle Scholar
  29. Gouldson P, Calandra B, Legoux P, Kerneis A, Rinaldi-Carmona M, Barth F, Le Fur G, Ferrara P, Shire D (2000) Mutational analysis and molecular modelling of the antagonist SR 144528 binding site on the human cannabinoid CB2 receptor. Eur J Pharmacol 401:17–25.CrossRefPubMedGoogle Scholar
  30. Gudermann T, Schoneberg T, Schultz G (1997) Functional and structural complexity of signal transduction via G protein-coupled receptors. Annu Rev Neurosci 20:399–427.CrossRefPubMedGoogle Scholar
  31. Guzman M, Galve-Roperh I, Sanchez C (2001) Ceramide: a new second messenger of cannabinoid action. Trends Pharmacol Sci 22:19–22.CrossRefPubMedGoogle Scholar
  32. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–1936.CrossRefPubMedGoogle Scholar
  33. Herrera B, Carracedo A, Diez-Zaera M, Gomez del Pulgar T, Guzman M, Velasco G (2006) The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Exp Cell Res 312:2121–2131.CrossRefPubMedGoogle Scholar
  34. Howlett AC (1985) Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. Mol Pharm 27:429–436.Google Scholar
  35. Howlett AC (1995) Pharmacology of cannabinoid receptors. Annu Rev Pharmacol Toxicol 35:607–634.CrossRefPubMedGoogle Scholar
  36. Howlett AC, Mukhopadhyay S (2000) Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem Phys Lipids 108:53–70.CrossRefPubMedGoogle Scholar
  37. Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan Jr TP (2003) Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci USA 100:10529–10533.CrossRefPubMedGoogle Scholar
  38. Ishac E, Jiang L, Lake K, Varga K, Abood M, Kunos G (1996) Inhibition of exocytotic noradrenaline release by presynaptic CB1 receptors on peripheral sympathetic nerves. Br J Pharmacol 118:2023–2028.PubMedGoogle Scholar
  39. Iversen L, Chapman V (2002) Cannabinoids: a real prospect for pain relief. Curr Opin Pharmacol 2:50–55.CrossRefPubMedGoogle Scholar
  40. Jorda MA, Verbakel SE, Valk PJ, Vankan-Berkhoudt YV, Maccarrone M, Finazzi-Agro A, Lowenberg B, Delwel R (2002) Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood 99:2786–2793.CrossRefPubMedGoogle Scholar
  41. Kaminski NE, Koh WS, Yang KH, Lee M, Kessler FK (1994) Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G protein-coupled mechanism. Biochem Pharmacol 48:1899–1908.CrossRefPubMedGoogle Scholar
  42. Kaplan BL, Rockwell CE, Kaminski NE (2003) Evidence for cannabinoid receptor-dependent and -independent mechanisms of action in leukocytes. J Pharmacol Exp Ther 306:1077–1085.CrossRefPubMedGoogle Scholar
  43. Kenakin T (2001) Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J 15:598–611.CrossRefPubMedGoogle Scholar
  44. Kenakin T (2002) Drug efficacy at G protein-coupled receptors. Annu Rev Pharmacol Toxicol 42:349–379.CrossRefPubMedGoogle Scholar
  45. Kishimoto S, Gokoh M, Oka S, Muramatsu M, Kajiwara T, Waku K, Sugiura T (2003) 2-arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism. J Biol Chem 278:24469–24475.CrossRefPubMedGoogle Scholar
  46. Klein T, Newton C, Larsen K, Lu L, Perkins I, Liang N, Friedman H (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486–496.CrossRefPubMedGoogle Scholar
  47. Kobayashi Y, Arai S, Waku K, Sugiura T (2001) Activation by 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, of p42/44 mitogen-activated protein kinase in HL-60 cells. J Biochem 129:665–669.PubMedGoogle Scholar
  48. Lunn CA, Fine JS, Rojas-Triana A, Jackson JV, Fan X, Kung TT, Gonsiorek W, Schwarz MA, Lavey B, Kozlowski JA, Narula SK, Lundell DJ, Hipkin RW, Bober LA (2006) A novel cannabinoid peripheral cannabinoid receptor-selective inverse agonist blocks leukocyte recruitment in vivo. J Pharmacol Exp Ther 316:780–788.Google Scholar
  49. Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89:3825–3829.CrossRefPubMedGoogle Scholar
  50. Mackie K, Lai Y, Westenbroek R, Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15:6552–6561.PubMedGoogle Scholar
  51. Maekawa T, Nojima H, Kuraishi Y, Aisaka K (2006) The cannabinoid CB2 receptor inverse agonist JTE-907 suppresses spontaneous itch-associated responses of NC mice, a model of atopic dermatitis. Eur J Pharmacol 542:179–183.CrossRefPubMedGoogle Scholar
  52. Maneuf YP, Brotchie JM (1997) Paradoxical action of the cannabinoid WIN 55, 212–2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices. Br J Pharmacol 120:1397–1398.CrossRefPubMedGoogle Scholar
  53. Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN (2005) Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 95:437–445.CrossRefPubMedGoogle Scholar
  54. Matsuda L, Lolait S, Brownstein M, Young A, Bonner T (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564.CrossRefPubMedGoogle Scholar
  55. McAllister SD, Griffin G, Satin LS, Abood ME (1999) Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J Pharmacol Exp Ther 291:618–626.PubMedGoogle Scholar
  56. Molina-Holgado E, Vela JM, Arevalo-Martin A, Almazan G, Molina-Holgado F, Borrell J, Guaza C (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22:9742–9753.PubMedGoogle Scholar
  57. Molina-Holgado F, Pinteaux E, Heenan L, Moore JD, Rothwell NJ, Gibson RM (2005) Neuroprotective effects of the synthetic cannabinoid HU-210 in primary cortical neurons are mediated by phosphatidylinositol 3-kinase/Akt signaling. Mol Cell Neurosci 28:189–194.CrossRefPubMedGoogle Scholar
  58. Mukhopadhyay S, Das S, Williams EA, Moore D, Jones JD, Zahm DS, Ndengele MM, Lechner AJ, Howlett AC (2006) Lipopolysaccharide and cyclic AMP regulation of CB2 cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages. J Neuroimmunol 181:82–92.CrossRefPubMedGoogle Scholar
  59. Munro S, Thomas K, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65.CrossRefPubMedGoogle Scholar
  60. Oka S, Ikeda S, Kishimoto S, Gokoh M, Yanagimoto S, Waku K, Sugiura T (2004) 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces the migration of EoL-1 human eosinophilic leukemia cells and human peripheral blood eosinophils. J Leukoc Biol 76:1002–1009.CrossRefPubMedGoogle Scholar
  61. Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA, Myers L, Mora Z, Tagliaferro P, Gardner E, Brusco A, Akinshola BE, Liu QR, Hope B, Iwasaki S, Arinami T, Teasenfitz L, Uhl GR (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514–536.CrossRefPubMedGoogle Scholar
  62. Prather PL (2004) Inverse agonists: tools to reveal ligand-specific conformations of G protein-coupled receptors. Sci STKE 2004:1.CrossRefGoogle Scholar
  63. Racz I, Bilkei-Gorzo A, Toth Z, Michel K, Palkovits M, Zimmer A (2003) A critical role for the cannabinoid CB1 receptors in alcohol dependence and stress-stimulated ethanol drinking. J Neurosci 23:2453–2458.PubMedGoogle Scholar
  64. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML (2005) Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25:1904–1913.CrossRefPubMedGoogle Scholar
  65. Ravinet T, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand J, Soubrie P (2002) Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 284:345–353.Google Scholar
  66. Rayman N, Lam KH, Laman JD, Simons PJ, Lowenberg B, Sonneveld P, Delwel R (2004) Distinct expression profiles of the peripheral cannabinoid receptor in lymphoid tissues depending on receptor activation status. J Immunol 172:2111–2117.PubMedGoogle Scholar
  67. Sanchez C, de Ceballos ML, del Pulgar TG, Rueda D, Corbacho C, Velasco G, Galve-Roperh I, Huffman JW, Ramon y Cajal S, Guzman M (2001) Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Res 61:5784–5789.PubMedGoogle Scholar
  68. Sanchez MG, Ruiz-Llorente L, Sanchez AM, Diaz-Laviada I (2003) Activation of phosphoinositide 3-kinase/PKB pathway by CB1 and CB2 cannabinoid receptors expressed in prostate PC-3 cells. Involvement in Raf-1 stimulation and NGF induction. Cell Signal 15:851–859.CrossRefPubMedGoogle Scholar
  69. Scott D, Wright C, Angus J (2004) Evidence that CB1 and CB2 cannabinoid receptors mediate antinoception in neuropathic pain in the rat. Pain 109:124–131.CrossRefPubMedGoogle Scholar
  70. Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessegue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P (1996) Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Acta 1307:132–136.PubMedGoogle Scholar
  71. Shoemaker JL, Joseph BK, Ruckle MB, Mayeux PR, Prather PL (2005a) The endocannabinoid noladin ether acts as a full agonist at human CB2 cannabinoid receptors. J Pharmacol Exp Ther 314:868–875.CrossRefPubMedGoogle Scholar
  72. Shoemaker JL, Ruckle MB, Mayeux PR, Prather PL (2005b) Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J Pharmacol Exp Ther 315:828–838.CrossRefPubMedGoogle Scholar
  73. Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL (2007) The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J Neurochem 101:87–98.CrossRefPubMedGoogle Scholar
  74. Sim-Selley LJ (2003) Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Crit Rev Neurobiol 15:91–119.CrossRefPubMedGoogle Scholar
  75. Slipetz DM, O’Neill GP, Favreau L, Dufresne C, Gallant M, Gareau Y, Guay D, Labelle M, Metters KM (1995) Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase. Mol Pharm 48:352–361.Google Scholar
  76. Soderstrom K, Johnson F (2000) CB1 cannabinoid receptor expression in brain regions associated with zebra finch song control. Brain Res 857:151–157.CrossRefPubMedGoogle Scholar
  77. Soderstrom K, Leid M, Moore FL, Murray TF (2000) Behavioral, pharmacological, and molecular characterization of an amphibian cannabinoid receptor. J Neurochem 75:413–423.CrossRefPubMedGoogle Scholar
  78. Song ZH, Slowey CA, Hurst DP, Reggio PH (1999) The difference between the CB1 and CB2 cannabinoid receptors at position 5.46 is crucial for the selectivity of WIN55212–2 for CB2. Mol Pharm 56:834–840.Google Scholar
  79. Strange PG (2002) Mechanisms of inverse agonism at G protein-coupled receptors. Trends Pharmacol Sci 23:89–95.CrossRefPubMedGoogle Scholar
  80. Sugiura T, Kodaka T, Kondo S, Nakane S, Kondo H, Waku K, Ishima Y, Watanabe K, Yamamoto I (1997) Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108–15 cells. J Biochem 122:890–895.PubMedGoogle Scholar
  81. Sugiura T, Kondo S, Kishimoto S, Miyashita T, Nakane S, Kodaka T, Suhara Y, Takayama H, Waku K (2000) Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells. J Biol Chem 275:605–612.CrossRefPubMedGoogle Scholar
  82. Tao Q, McAllister SD, Andreassi J, Nowell KW, Cabral GA, Hurst DP, Bachtel K, Ekman MC, Reggio PH, Abood ME (1999) Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity. Mol Pharm 55:605–613.Google Scholar
  83. Tuccinardi T, Ferrarini PL, Manera C, Ortore G, Saccomanni G, Martinelli A (2006) Cannabinoid CB2 /CB1 selectivity. Receptor modeling and automated docking analysis. J Med Chem 49:984–994.CrossRefPubMedGoogle Scholar
  84. Ueda Y, Miyagawa N, Wakitani K (2007) Involvement of cannabinoid CB2 receptors in the IgE-mediated triphasic cutaneous reaction in mice. Life Sci 80:414–419.CrossRefPubMedGoogle Scholar
  85. Valk PJ, Hol S, Vankan Y, Ihle JN, Askew D, Jenkins NA, Gilbert DJ, Copeland NG, de Both NJ, Lowenberg B, Delwel R (1997) The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are located near a newly identified common virus integration site, Evi11. J Virol 71:6796–6804.PubMedGoogle Scholar
  86. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332.CrossRefPubMedGoogle Scholar
  87. Vasquez C, Lewis DL (1999) The CB1 cannabinoid receptor can sequester G proteins, making them unavailable to couple to other receptors. J Neurosci 19:9271–9280.PubMedGoogle Scholar
  88. 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
  89. Wiens BL, Nelson CS, Neve KA (1998) Contribution of serine residues to constitutive and agonist-induced signaling via the D2S dopamine receptor: evidence for multiple, agonist-specific active conformations. Mol Pharm 54:435–444.Google Scholar
  90. Yamaguchi F, Macrae AD, Brenner S (1996) Molecular cloning of two cannabinoid type 1-like receptor genes from the puffer fish Fugu rubripes. Genomics 35:603–605.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Paul L. Prather
    • 1
  1. 1.Dept of Pharmacology & Toxicology, Mail Slot 611College of Medicine University of Arkansas for Medical Sciences

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