Cannabinoid receptor 2
Template:PBB 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][2] 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 marijuana, and other phytocannabinoids (natural cannabinoids).[1][3] The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG).[2]
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.[1] 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.[1][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.[1] 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
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.[16] These receptors were primarily localized on immune cells such as monocytes, macrophages, B-cells, and T-cells.[2][6][17][18][19]
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.[20] Unlike the CB1 receptor, in the brain, CB2 receptors are found primarily on microglia, but not neurons.[16][21]
Gastrointestinal System
CB2 receptors are also found throughout the gastrointestinal system, where they modulate intestinal inflammatory response.[22][23] Thus, CB2 receptor is a potential therapeutic target for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis.[23][24] 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.[25] Cannabinoid receptor agonists reduce gut motility in IBS patients.[26]
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.[27] 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.[2] 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).[28][29] 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.[27] This reduction causes changes in the expression of critical immunoregulatory genes[28] and ultimately suppression of immune function.[29]
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.[30] 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.[31]
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.[2] Together, these findings demonstrate that the endocannabinoid system maybe 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.[32][33] Specifically, the CB2 agonist JWH-015 was shown to induce macrophages to remove native beta-amyloid protein from frozen human tissues.[34] In patient's with Alzheimer's disease, beta-amyloid proteins form aggregates known as senile plaques, which disrupt neural functioning.[35]
Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[36] 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 [36]
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.[citation needed]
Ligands
Many selective ligands for the CB2 receptor are now available.[37]
Partial agonists
Unspecified efficacy agonists
Herbal
Inverse agonists
Binding affinities
CB1 affinity (Ki) | Efficacy towards CB1 | CB2 affinity (Ki) | Efficacy towards CB2 | Type | References | |
---|---|---|---|---|---|---|
Anandamide | 78 nM | Full agonist | 370 nM | Partial agonist | Endogenous | |
N-Arachidonoyl dopamine | 250 nM | Agonist | 12000 nM | ? | Endogenous | [38] |
2-Arachidonoylglycerol | 58.3 nM | Full agonist | 145 nM | Full agonist | Endogenous | [38] |
2-Arachidonyl glyceryl ether | 21 nM | Full agonist | 480 nM | Full agonist | Endogenous | |
Tetrahydrocannabinol | 10 nM | Partial agonist | 24 nM | Partial agonist | Phytogenic | [39][39] |
EGCG | 33.6 μM | Agonist | >50 μM | ? | Phytogenic | |
AM-1221 | 52.3 nM | Agonist | 0.28 nM | Agonist | Synthetic | [40] |
AM-1235 | 1.5 nM | Agonist | 20.4 nM | Agonist | Synthetic | [41] |
AM-2232 | 0.28 nM | Agonist | 1.48 nM | Agonist | Synthetic | [41] |
UR-144 | 150 nM | Full agonist | 1.8 nM | Full agonist | Synthetic | [42] |
JWH-007 | 9.0 nM | Agonist | 2.94 nM | Agonist | Synthetic | [43] |
JWH-015 | 383 nM | Agonist | 13.8 nM | Agonist | Synthetic | [43] |
JWH-018 | 9.00 ± 5.00 nM | Full agonist | 2.94 ± 2.65 nM | Full agonist | Synthetic | [44] |
See also
References
- ^ a b c d e Munro S, Thomas KL, Abu-Shaar M (September 1993). "Molecular characterization of a peripheral receptor for cannabinoids". Nature. 365 (6441): 61–5. doi:10.1038/365061a0. PMID 7689702.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid7689702" was defined multiple times with different content (see the help page). - ^ a b c d e Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22048769, please use {{cite journal}} with
|pmid=22048769
instead. - ^ "Entrez Gene: CNR2 cannabinoid receptor 2 (macrophage)".
- ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11316486, please use {{cite journal}} with
|pmid=11316486
instead. - ^ a b c d e Cabral GA, Griffin-Thomas L. (2009). "Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation". Expert Rev Mol Med. 11: e3. doi:10.1017/S1462399409000957. PMC 2768535. PMID 19152719.
- ^ a b c d e Sylvaine G, Sophie M, Marchand J, Dussossoy D, Carriere D, Carayon P, Monsif B, 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 (1): 54–61. doi:10.1111/j.1432-1033.1995.tb20780.x. PMID 7556170.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid7556170" was defined multiple times with different content (see the help page). - ^ Griffin G, Tao Q, Abood ME (2000). "Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor". J Pharmacol Exp Ther. 292 (3): 886–894. PMID 10688601.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c 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 (3): 984–994. doi:10.1021/jm050875u. PMID 16451064.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c d e Shoemaker JL, Ruckle MB, Mayeux PR, Prather PL (2005). "Agonist-Directed Trafficking of Response by Endocannabinoids Acting at CB2 Receptors". J Pharmacol Exp Ther. 315 (2): 828–838. doi:10.1124/jpet.105.089474. PMID 16081674.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Demuth DG, Molleman A. (2006). "Cannabinoid Signalling". Life Sci. 78 (6): 549–563. doi:10.1016/j.lfs.2005.05.055. PMID 16109430.
- ^ a b Bouaboula M, Poinot-Chazel C, Marchand J, Canat X, Bourrié B, Rinaldi-Carmona M, Calandra B, Le Fur G, Casellas P. (19966). "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 (3): 704–711. doi:10.1111/j.1432-1033.1996.0704p.x. PMID 8647116.
{{cite journal}}
: Check date values in:|year=
(help)CS1 maint: multiple names: authors list (link) CS1 maint: year (link) - ^ Shvartsman SY, Coppey M, Berezhkovskii AM (2009). "MAPK signaling in equations and embryos". Fly (Austin). 3 (1): 62–7. doi:10.4161/fly.3.1.7776. PMC 2712890. PMID 19182542.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Klemke RL, Cai S, Gianni AL, Gallagher PJ, Lanerolle P, Cheresh DA. (1997). "Regulation of Cell Motility by Mitogen-activated Protein Kinase". J Cell Bio. 137 (2): 481–492. doi:10.1083/jcb.137.2.481. PMC 2139771. PMID 9128257.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Alberini CM. (2009). "Transcription factors in long-term memory and synaptic plasticity". Physiol Rev. 89 (1): 121–145. doi:10.1152/physrev.00017.2008. PMID 19126756.
- ^ Bisogno T, Melck D, Bobrov MYu, Gretskaya NM, Bezuglov VV, De Petrocellis L, Di Marzo V (November 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. 351 (3): 817–24. doi:10.1042/0264-6021:3510817. PMC 1221424. PMID 11042139.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16570099, please use {{cite journal}} with
|pmid=16570099
instead. - ^ Miller AM, Stella N (January 2008). "CB2 receptor-mediated migration of immune cells: it can go either way". Br. J. Pharmacol. 153 (2): 299–308. doi:10.1038/sj.bjp.0707523. PMC 2219538. PMID 17982478.
- ^ Ashton JC, Glass M (June 2007). "The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration". Curr Neuropharmacol. 5 (2): 73–80. doi:10.2174/157015907780866884. PMC 2435344. PMID 18615177.
- ^ Centonze D, Battistini L, Maccarrone M (2008). "The endocannabinoid system in peripheral lymphocytes as a mirror of neuroinflammatory diseases". Curr. Pharm. Des. 14 (23): 2370–42. doi:10.2174/138161208785740018. PMID 18781987.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Onaivi ES (2006). "Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain". Neuropsychobiology. 54 (4): 231–46. doi:10.1159/000100778. PMID 17356307.
- ^ Cabral GA, Raborn ES, Griffin L, Dennis J, Marciano-Cabral F (January 2008). "CB2 receptors in the brain: role in central immune function". Br. J. Pharmacol. 153 (2): 240–51. doi:10.1038/sj.bjp.0707584. PMC 2219530. PMID 18037916.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Izzo AA.; Ho, W; Pittman, QJ; Davison, JS; Sharkey, KA (2004). "Cannabinoids and intestinal motility: welcome to CB2 receptors". Br J Pharmacol. 142 (8): 1247–54. doi:10.1038/sj.bjp.0705890. PMC 1575197. PMID 15277313.
- ^ a b Wright KL, Duncan M, Sharkey KA. (2008). "Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation". Br J Pharmacol. 153 (2): 263–70. doi:10.1038/sj.bjp.0707486. PMC 2219529. PMID 17906675.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C, Capasso F, Izzo AA. (2008). "Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice". Br J Pharmacol. 154 (5): 1001–8. doi:10.1038/bjp.2008.177. PMC 2451037. PMID 18469842.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ "The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome". Neurogastroenterol Motil. Aug 2008. PMID 18710476.
- ^ "Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome". Gastroenterology. Nov 2011. PMID 21803011.
- ^ a b Kaminski NE. (1998). "Inhibition of the cAMP signaling cascade via cannabinoid receptors: a putative mechanism of immune modulation by cannabinoid compounds". Toxicol Lett. 102–103: 59–63. doi:10.1016/S0378-4274(98)00284-7. PMID 10022233.
- ^ a b Herring AC, Koh WS, Kaminski NE. (1998). "Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE and kappaB elements by cannabinol, a minimally CNS-active cannabinoid". Biochem Pharmacol. 55 (7): 1013–23. doi:10.1016/S0006-2952(97)00630-8. PMID 9605425.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Kaminski NE. (1996). "Immune regulation by cannabinoid compounds through the inhibition of the cyclic AMP signaling cascade and altered gene expression". Biochem Pharmacol. 52 (8): 1133–40. doi:10.1016/0006-2952(96)00480-7. PMID 8937419.
- ^ Cheng Y, Hitchcock SA (July 2007). "Targeting cannabinoid agonists for inflammatory and neuropathic pain". Expert Opin Investig Drugs. 16 (7): 951–65. doi:10.1517/13543784.16.7.951. PMID 17594182.
- ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 17828291, please use {{cite journal}} with
|pmid=17828291
instead. - ^ Benito C, Núñez E, Tolón RM; et al. (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 (35): 11136–41. PMID 14657172.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Fernández-Ruiz J, Pazos MR, García-Arencibia M, Sagredo O, Ramos JA (April 2008). "Role of CB2 receptors in neuroprotective effects of cannabinoids". Mol. Cell. Endocrinol. 286 (1–2 Suppl 1): S91–6. doi:10.1016/j.mce.2008.01.001. PMID 18291574.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Tolón RM, Núñez E, Pazos MR, Benito C, Castillo AI, Martínez-Orgado JA, Romero J. (2009). "The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages". Brain Res. 62 (11): 1984–9. doi:10.1016/j.brainres.2009.05.098. PMID 19505450.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. (2004). "The importance of neuritic plaques and tangles to the development and evolution of AD". Neurology. 62 (11): 1984–9. doi:10.1212/01.WNL.0000129697.01779.0A. PMID 15184601.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Pacher P, Mechoulam R (2011). "Is lipid signaling through cannabinoid 2 receptors part of a protective system?". Prog Lipid Res. 50 (2): 193–211. doi:10.1016/j.plipres.2011.01.001. PMC 3062638. PMID 21295074.
- ^ Marriott KS, Huffman JW (2008). "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". Curr Top Med Chem. 8 (3): 187–204. doi:10.2174/156802608783498014. PMID 18289088.
- ^ a b Pertwee RG, Howlett AC, Abood ME, Alexander SPH, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross AR (2010). "International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2". Pharmacol. Rev. 62 (4): 588–631. doi:10.1124/pr.110.003004. PMID 21079038.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b "PDSP Database - UNC". Retrieved 11 June 2013.
- ^ WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07
- ^ a b US patent 7241799, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2007-07-10
- ^ 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 (January 2010). "Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity". J. Med. Chem. 53 (1): 295–315. doi:10.1021/jm901214q. PMID 19921781.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (August 2000). "Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2)receptor binding". Drug Alcohol Depend. 60 (2): 133–40. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (August 2000). "Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding". Drug Alcohol Depend. 60 (2): 133–40. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)
External links
- "Cannabinoid Receptors: CB2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Further reading
- Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/sj.bjp.0707523, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1038/sj.bjp.0707523
instead.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.