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词条 Cannabinoid receptor type 2
释义

  1. Structure

  2. Mechanism

  3. Expression

      Dispute    Immune system    Brain    Gastrointestinal system    Peripheral nervous system  

  4. Function

      Immune system    Clinical applications    Modulation of cocaine reward  

  5. Ligands

      Agonists    Partial agonists    Unspecified efficacy agonists    Herbal    Inverse agonists  

  6. Binding affinities

  7. See also

  8. References

  9. Further reading

  10. External links

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The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene.[1][1] It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol, the active agent in cannabis, and other phytocannabinoids (plant cannabinoids).[2][3] The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG).[1]

CB2 was cloned in 1993 by a research group from Cambridge looking for a second cannabinoid receptor that could explain the pharmacological properties of tetrahydrocannabinol.[2] The receptor was identified among cDNAs based on its similarity in amino-acid sequence to the cannabinoid receptor type 1 (CB1) receptor, discovered in 1990.[4] The discovery of this receptor helped provide a molecular explanation for the established effects of cannabinoids on the immune system.

Structure

The CB2 receptor is encoded by the CNR2 gene.[2][5] Approximately 360 amino acids comprise the human CB2 receptor, making it somewhat shorter than the 473-amino-acid-long CB1 receptor.[5]

As is commonly seen in G protein-coupled receptors, the CB2 receptor has seven transmembrane spanning domains,[6] a glycosylated N-terminus, and an intracellular C-terminus.[5] The C-terminus of CB2 receptors appears to play a critical role in the regulation of ligand-induced receptor desensitization and downregulation following repeated agonist application,[5] perhaps causing the receptor to become less responsive to particular ligands.

The human CB1 and the CB2 receptors possess approximately 44% amino acid similarity.[2] When only the transmembrane regions of the receptors are considered, however, the amino acid similarity between the two receptor subtypes is approximately 68%.[5] The amino acid sequence of the CB2 receptor is less highly conserved across human and rodent species as compared to the amino acid sequence of the CB1 receptor.[7] Based on computer modeling, ligand interactions with CB2 receptor residues S3.31 and F5.46 appears to determine differences between CB1 and CB2 receptor selectivity.[8] In CB2 receptors, lipophilic groups interact with the F5.46 residue, allowing them to form a hydrogen bond with the S3.31 residue.[8] These interactions induce a conformational change in the receptor structure, which triggers the activation of various intracellular signaling pathways. Further research is needed to determine the exact molecular mechanisms of signaling pathway activation.[8]

Mechanism

Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]

At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors.

Expression

Dispute

Originally it was thought that the CB2 receptor was only expressed in peripheral tissue while the CB1 receptor is the endogenous receptor on neurons. Recent work with immunohistochemical staining has shown expression within neurons. Subsequently, it was shown that CB2 knock out mice, produced the same immunohistochemical staining, indicating the presence of the CB2 receptor where none was expressed. This has created a long history of debate as to the Central Nervous System expression of the CB2 receptor. A new mouse model was described in 2014 that expresses a fluorescent protein whenever CB2 is expressed within a cell. This has the potential to resolve questions about the expression of CB2 receptors in various tissues.[16]

Immune system

Initial investigation of CB2 receptor expression patterns focused on the presence of CB2 receptors in the peripheral tissues of the immune system [6] and found CB2 receptor mRNA is found throughout tissues of the spleen, tonsils, and thymus gland.[6] Northern blot analysis further indicates the expression of the CNR2 gene in immune tissues,[6] where they are primarily responsible for mediating cytokine release.[17] These receptors were primarily localized on immune cells such as monocytes, macrophages, B-cells, and T-cells.[1][6][18][19][20]

Brain

Further investigation into the expression patterns of the CB2 receptors revealed that CB2 receptor gene transcripts are also expressed in the brain, though not as densely as the CB1 receptor and located on different cells.[21] Unlike the CB1 receptor, in the brain, CB2 receptors are found primarily on microglia.[17][22] The CB2 receptor is expressed in some neurons within the central nervous system (e.g.; the brainstem), but the expression is very low.[23][24] CB2Rs are expressed on some rat retinal cell types.[25] Functional CB2 receptors are expressed in neurons of the ventral tegmental area and the hippocampus, arguing for a widespread expression and functional relevance in the CNS and in particular in neuronal signal transmission.[26][27]

Gastrointestinal system

CB2 receptors are also found throughout the gastrointestinal system, where they modulate intestinal inflammatory response.[28][29] Thus, CB2 receptor is a potential therapeutic target for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis.[29][30] The role of endocannabinoids, as such, play an important role in inhibiting unnecessary immune action upon the natural gut flora. Dysfunction of this system, perhaps from excess FAAH activity, could result in IBD. CB2 activation may also have a role in the treatment of irritable bowel syndrome.[31] Cannabinoid receptor agonists reduce gut motility in IBS patients.[32]

Peripheral nervous system

Application of CB2-specific antagonists has found that these receptors are also involved in mediating analgesic effects in the peripheral nervous system. However, these receptors are not expressed by nociceptive sensory neurons, and at present are believed to exist on an undetermined, non-neuronal cell. Possible candidates include mast cells, known to facilitate the inflammatory response. Cannabinoid mediated inhibition of these responses may cause a decrease in the perception of noxious-stimuli.[4]

Function

Immune system

Primary research on the functioning of the CB2 receptor has focused on the receptor's effects on the immunological activity of leukocytes.[33] To be specific, this receptor has been implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, and induction of cell migration.[1] Through their inhibition of adenylyl cyclase via their Gi/Goα subunits, CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP).[34][35] Although the exact role of the cAMP cascade in the regulation of immune responses is currently under debate, laboratories have previously demonstrated that inhibition of adenylyl cyclase by CB2 receptor agonists results in a reduction in the binding of transcription factor CREB (cAMP response element-binding protein) to DNA.[33] This reduction causes changes in the expression of critical immunoregulatory genes[34] and ultimately suppression of immune function.[35]

Later studies examining the effect of synthetic cannabinoid agonist JWH-015 on CB2 receptors revealed that changes in cAMP levels result in the phosphorylation of leukocyte receptor tyrosine kinase at Tyr-505, leading to an inhibition of T cell receptor signaling. Thus, CB2 agonists may also be useful for treatment of inflammation and pain, and are currently being investigated, in particular for forms of pain that do not respond well to conventional treatments, such as neuropathic pain.[36] Consistent with these findings are studies that demonstrate increased CB2 receptor expression in the spinal cord, dorsal root ganglion, and activated microglia in the rodent neuropathic pain model, as well as on human heptocellular carcinoma tumor samples.[37]

CB2 receptors have also been implicated in the regulation of homing and retention of marginal zone B cells. A study using knock-out mice found that CB2 receptor is essential for the maintenance of both MZ B cells and their precursor T2-MZP, though not their development. Both B cells and their precursors lacking this receptor were found in reduced numbers, explained by the secondary finding that 2-AG signaling was demonstrated to induce proper B cell migration to the MZ. Without the receptor, there was an undesirable spike in the blood concentration of MZ B lineage cells and a significant reduction in the production of IgM. While the mechanism behind this process is not fully understood, the researchers suggested that this process may be due to the activation-dependent decrease in cAMP concentration, leading to reduced transcription of genes regulated by CREB, indirectly increasing TCR signaling and IL-2 production.[1] Together, these findings demonstrate that the endocannabinoid system may be exploited to enhance immunity to certain pathogens and autoimmune diseases.

Clinical applications

CB2 receptors may have possible therapeutic roles in the treatment of neurodegenerative disorders such as Alzheimer's disease.[38][39] Specifically, the CB2 agonist JWH-015 was shown to induce macrophages to remove native beta-amyloid protein from frozen human tissues.[40] In patients with Alzheimer's disease, beta-amyloid proteins form aggregates known as senile plaques, which disrupt neural functioning.[41]

Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[42] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [42]

Modulation of cocaine reward

Researchers investigated the effects of CB2 agonists on cocaine self-administration in mice. Systemic administration of JWH-133 reduced the number of self-infusions of cocaine in mice, as well as reducing locomotor activity and the break point (maximum amount of level presses to obtain cocaine). Local injection of JWH-133 into the nucleus accumbens was found to produce the same effects as systemic administration. Systemic administration of JWH-133 also reduced basal and cocaine-induced elevations of extracellular dopamine in the nucleus accumbens. These findings were mimicked by another, structurally different CB2 agonist, GW-405,833, and were reversed by the administration of a CB2 antagonist, AM-630.[43]

Ligands

Many selective ligands for the CB2 receptor are now available.[44]

Agonists

  • Minocycline[45]

Partial agonists

  • GW-405,833

Unspecified efficacy agonists

  • AM-1241
  • HU-308
  • JWH-015
  • JWH-133
  • L-759,633
  • L-759,656

Herbal

  • Echinacea purpurea

Inverse agonists

  • AM-630
  • BML-190
  • JTE-907
  • SR-144,528

Binding affinities

CB1 affinity (Ki) Efficacy towards CB1 CB2 affinity (Ki) Efficacy towards CB2 Type References
Anandamide 78 nM Partial agonist 370 nM Partial agonist Endogenous
N-Arachidonoyl dopamine 250 nM Agonist 12000 nM ? Endogenous[46]
2-Arachidonoylglycerol 58.3 nM Full agonist 145 nM Full agonist Endogenous[46]
2-Arachidonyl glyceryl ether 21 nM Full agonist 480 nM Full agonist Endogenous
Tetrahydrocannabinol 10 nM Partial agonist 24 nM Partial agonist Phytogenic [47][47]
EGCG 33.6 μM Agonist >50 μM ? Phytogenic[48]
EGC35.7 μMAgonist>50 μM?Phytogenic[48]
ECG47.3 μMAgonist>50 μM?Phytogenic[48]
N-alkylamide - -<100 nMPartial agonistPhytogenic[84][49]
β-Caryophyllene - -<200 nMFull agonistPhytogenic[49]
Falcarinol<1 μMInverse agonist??Phytogenic[49]
Rutamarin - -<10 μM?Phytogenic[49]
3,3'-Diindolylmethane - -1 μMPartial AgonistPhytogenic[49]
AM-1221 52.3 nM Agonist 0.28 nM Agonist Synthetic [50]
AM-1235 1.5 nM Agonist 20.4 nM Agonist Synthetic [51]
AM-2232 0.28 nM Agonist 1.48 nM Agonist Synthetic [51]
UR-144 150 nM Full agonist 1.8 nM Full agonist Synthetic [52]
JWH-007 9.0 nM Agonist 2.94 nM Agonist Synthetic [53]
JWH-015 383 nM Agonist 13.8 nM Agonist Synthetic [53]
JWH-018 9.00 ± 5.00 nM Full agonist 2.94 ± 2.65 nM Full agonist Synthetic [53]

See also

  • Cannabinoid receptor
  • Cannabinoid receptor type 1 (CB1)

References

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43. ^{{Cite journal|last=Xi|first=Zheng-Xiong|last2=Peng|first2=Xiao-Qing|last3=Li|first3=Xia|last4=Song|first4=Rui|last5=Zhang|first5=Haiying|last6=Liu|first6=Qing-Rong|last7=Yang|first7=Hong-Ju|last8=Bi|first8=Guo-Hua|last9=Li|first9=Jie|date=2011-07-24|title=Brain Cannabinoid CB2 Receptors Modulate Cocaine's Actions in Mice|journal=Nature Neuroscience|volume=14|issue=9|pages=1160–1166|doi=10.1038/nn.2874|issn=1097-6256|pmc=3164946|pmid=21785434}}
44. ^{{cite journal | vauthors = Marriott KS, Huffman JW | title = Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor | journal = Current Topics in Medicinal Chemistry | volume = 8 | issue = 3 | pages = 187–204 | year = 2008 | pmid = 18289088 | doi = 10.2174/156802608783498014 | url = http://www.bentham-direct.org/pages/content.php?CTMC/2008/00000008/00000003/0003R.SGM | access-date = 2018-11-19 | archive-url = https://archive.is/20130112141316/http://www.bentham-direct.org/pages/content.php?CTMC/2008/00000008/00000003/0003R.SGM# | archive-date = 2013-01-12 | dead-url = yes | df = }}
45. ^{{cite journal |title=CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice |date=2015-01-01 |journal=Cereb. Cortex |doi=10.1093/cercor/bht202 |volume=25 |issue=1 |pages=35–45 |pmid=23960212 |author=Lopez-Rodriguez AB|display-authors=et al}}
46. ^1 {{cite journal | vauthors = Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA | title = International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂ | journal = Pharmacological Reviews | volume = 62 | issue = 4 | pages = 588–631 | date = Dec 2010 | pmid = 21079038 | doi = 10.1124/pr.110.003004 | pmc=2993256}}
47. ^1 {{cite web|title=PDSP Database - UNC|url=http://pdsp.med.unc.edu/pdsp.php?|accessdate=11 June 2013|deadurl=yes|archiveurl=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php|archivedate=8 November 2013|df=}}
48. ^1 2 {{cite journal | vauthors = Korte G, Dreiseitel A, Schreier P, Oehme A, Locher S, Geiger S, Heilmann J, Sand PG | title = Tea catechins' affinity for human cannabinoid receptors | journal = Phytomedicine | volume = 17 | issue = 1 | pages = 19–22 | date = Jan 2010 | doi = 10.1016/j.phymed.2009.10.001 | pmid = 19897346 }}
49. ^1 2 3 4 5 {{cite journal | vauthors = Gertsch J, Pertwee RG, Di Marzo V | title = Phytocannabinoids beyond the Cannabis plant - do they exist? | journal = British Journal of Pharmacology | volume = 160 | issue = 3 | pages = 523–9 | date = Jun 2010 | pmid = 20590562 | pmc = 2931553 | doi = 10.1111/j.1476-5381.2010.00745.x }}
50. ^{{Ref patent2 |country= WO |number= 200128557 |status= granted |title= Cannabimimetic indole derivatives |pubdate= 2001-04-26 |gdate= 2001-06-07 |pridate= 1999-10-18 |inventor= Makriyannis A, Deng H }}
51. ^1 {{Ref patent2 | country = US | number = 7241799 | status = granted | title = Cannabimimetic indole derivatives | pubdate = 2004-11-05 | gdate = 2007-07-10 | pridate= 2004-11-05 | inventor = Makriyannis A, Deng H | assign1= }}
52. ^{{cite journal | vauthors = Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD | title = Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 1 | pages = 295–315 | date = Jan 2010 | pmid = 19921781 | doi = 10.1021/jm901214q }}
53. ^1 2 {{cite journal | vauthors = Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR | title = Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding | journal = Drug and Alcohol Dependence | volume = 60 | issue = 2 | pages = 133–40 | date = Aug 2000 | pmid = 10940540 | doi = 10.1016/S0376-8716(99)00152-0 }}

Further reading

{{Refbegin | 2}}
  • {{cite book | vauthors = Oddi S, Spagnuolo P, Bari M, D'Agostino A, Maccarrone M | title = Differential modulation of type 1 and type 2 cannabinoid receptors along the neuroimmune axis | volume = 82 | pages = 327–37 | year = 2007 | pmid = 17678969 | doi = 10.1016/S0074-7742(07)82017-4 | isbn = 978-0-12-373989-6 | series = International Review of Neurobiology }}
  • {{cite journal | vauthors = Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P | title = Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations | journal = European Journal of Biochemistry / FEBS | volume = 232 | issue = 1 | pages = 54–61 | date = Aug 1995 | pmid = 7556170 | doi = 10.1111/j.1432-1033.1995.tb20780.x }}
  • {{cite journal | vauthors = Munro S, Thomas KL, Abu-Shaar M | title = Molecular characterization of a peripheral receptor for cannabinoids | journal = Nature | volume = 365 | issue = 6441 | pages = 61–5 | date = Sep 1993 | pmid = 7689702 | doi = 10.1038/365061a0 }}
  • {{cite journal | vauthors = Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessègue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P | title = Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor | journal = Biochimica et Biophysica Acta | volume = 1307 | issue = 2 | pages = 132–6 | date = Jun 1996 | pmid = 8679694 | doi = 10.1016/0167-4781(96)00047-4 }}
  • {{cite journal | vauthors = Tao Q, McAllister SD, Andreassi J, Nowell KW, Cabral GA, Hurst DP, Bachtel K, Ekman MC, Reggio PH, Abood ME | title = Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity | journal = Molecular Pharmacology | volume = 55 | issue = 3 | pages = 605–13 | date = Mar 1999 | pmid = 10051546 }}
  • {{cite book | vauthors = Nong L, Newton C, Friedman H, Klein TW |veditors=Friedman H, Klein TW, Madden JJ |chapter=CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types |title=Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases |volume=493 |pages=229–33 |year=2002 |pmid=11727770 |doi=10.1007/0-306-47611-8_27 |isbn=978-0-306-46466-9 |series=Advances in Experimental Medicine and Biology}}
  • {{cite journal | vauthors = Ho BY, Current L, Drewett JG | title = Role of intracellular loops of cannabinoid CB(1) receptor in functional interaction with G(alpha16) | journal = FEBS Letters | volume = 522 | issue = 1–3 | pages = 130–4 | date = Jul 2002 | pmid = 12095632 | doi = 10.1016/S0014-5793(02)02917-4 }}
  • {{cite journal | vauthors = Matias I, Pochard P, Orlando P, Salzet M, Pestel J, Di Marzo V | title = Presence and regulation of the endocannabinoid system in human dendritic cells | journal = European Journal of Biochemistry / FEBS | volume = 269 | issue = 15 | pages = 3771–8 | date = Aug 2002 | pmid = 12153574 | doi = 10.1046/j.1432-1033.2002.03078.x }}
  • {{cite journal | vauthors = Song ZH, Feng W | title = Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function | journal = FEBS Letters | volume = 531 | issue = 2 | pages = 290–4 | date = Nov 2002 | pmid = 12417328 | doi = 10.1016/S0014-5793(02)03537-8 }}
  • {{cite journal | vauthors = Casanova ML, Blázquez C, Martínez-Palacio J, Villanueva C, Fernández-Aceñero MJ, Huffman JW, Jorcano JL, Guzmán M | title = Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors | journal = The Journal of Clinical Investigation | volume = 111 | issue = 1 | pages = 43–50 | date = Jan 2003 | pmid = 12511587 | pmc = 151833 | doi = 10.1172/JCI16116 }}
  • {{cite journal | vauthors = Feng W, Song ZH | title = Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor | journal = Biochemical Pharmacology | volume = 65 | issue = 7 | pages = 1077–85 | date = Apr 2003 | pmid = 12663043 | doi = 10.1016/S0006-2952(03)00005-4 }}
  • {{cite journal | vauthors = Kishimoto S, Gokoh M, Oka S, Muramatsu M, Kajiwara T, Waku K, Sugiura T | title = 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 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 27 | pages = 24469–75 | date = Jul 2003 | pmid = 12711605 | doi = 10.1074/jbc.M301359200 }}
  • {{cite journal | vauthors = Jorda MA, Rayman N, Valk P, De Wee E, Delwel R | title = Identification, characterization, and function of a novel oncogene: the peripheral cannabinoid receptor Cb2 | journal = Annals of the New York Academy of Sciences | volume = 996 | pages = 10–6 | date = May 2003 | pmid = 12799277 | doi = 10.1111/j.1749-6632.2003.tb03227.x }}
  • {{cite journal | vauthors = Rayman N, Lam KH, Laman JD, Simons PJ, Löwenberg B, Sonneveld P, Delwel R | title = Distinct expression profiles of the peripheral cannabinoid receptor in lymphoid tissues depending on receptor activation status | journal = Journal of Immunology | volume = 172 | issue = 4 | pages = 2111–7 | date = Feb 2004 | pmid = 14764676 | doi = 10.4049/jimmunol.172.4.2111 }}
  • {{cite journal | vauthors = Rao GK, Zhang W, Kaminski NE | title = Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells | journal = Journal of Leukocyte Biology | volume = 75 | issue = 5 | pages = 884–92 | date = May 2004 | pmid = 14966196 | doi = 10.1189/jlb.1203638 }}
  • {{cite journal | vauthors = Alberich Jordà M, Rayman N, Tas M, Verbakel SE, Battista N, van Lom K, Löwenberg B, Maccarrone M, Delwel R | title = The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner | journal = Blood | volume = 104 | issue = 2 | pages = 526–34 | date = Jul 2004 | pmid = 15039279 | doi = 10.1182/blood-2003-12-4357 }}
  • {{cite journal | vauthors = Núñez E, Benito C, Pazos MR, Barbachano A, Fajardo O, González S, Tolón RM, Romero J | title = Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study | journal = Synapse | volume = 53 | issue = 4 | pages = 208–13 | date = Sep 2004 | pmid = 15266552 | doi = 10.1002/syn.20050 }}
  • {{cite journal | vauthors = Gokoh M, Kishimoto S, Oka S, Mori M, Waku K, Ishima Y, Sugiura T | title = 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells | journal = The Biochemical Journal | volume = 386 | issue = Pt 3 | pages = 583–9 | date = Mar 2005 | pmid = 15456404 | pmc = 1134878 | doi = 10.1042/BJ20041163 }}
  • {{Cite journal | doi = 10.1038/sj.bjp.0707523 | title = CB2receptor-mediated migration of immune cells: it can go either way | year = 2008 | last1 = Miller | first1 = A. M. | last2 = Stella | first2 = N. | journal = British Journal of Pharmacology | volume = 153 | pages = 299–308 | pmid = 17982478 | issue = 2 | pmc = 2219538 }}
  • {{cite journal | vauthors = López EM, Tagliaferro P, Onaivi ES, López-Costa JJ | title = Distribution of CB2 cannabinoid receptor in adult rat retina | journal = Synapse | volume = 65 | issue = 5 | pages = 388–92 | date = May 2011 | pmid = 20803619 | doi = 10.1002/syn.20856 }}
{{Refend}}

External links

  • {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2207 | title = Cannabinoid Receptors: CB2 | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
{{NLM content}}{{G protein-coupled receptors}}{{Cannabinoidergics}}{{DEFAULTSORT:Cannabinoid Receptor 2 (Macrophage)}}

1 : G protein-coupled receptors
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