The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Cnr1  -  cannabinoid receptor 1 (brain)

Mus musculus

Synonyms: Brain-type cannabinoid receptor, CB-R, CB1, CB1R, Cannabinoid receptor 1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Cnr1

  • Treatment with the CB1 receptor antagonist SR141716A decreased the wound-healing response to acute liver injury and inhibited progression of fibrosis in three models of chronic liver injury [1].
  • In conclusion, our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis [1].
  • DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis [2].
  • We used N1E-115 neuroblastoma cells and the cannabinoid receptor agonist WIN 55,212-2 (WIN) to examine the signal transduction pathways leading to the activation of ERK [3].
  • The EC50 for stimulation of ERK phosphorylation was 10 nm, and this effect was blocked by pertussis toxin and the CB1 (cannabinoid) receptor antagonist SR141716A [3].
  • LCB1(-/-) mice fed a high-fat diet developed a similar degree of obesity as that of wild-type mice, but, similar to CB1(-/-) mice, had less steatosis, hyperglycemia, dyslipidemia, and insulin and leptin resistance than did wild-type mice fed a high-fat diet [4].

Psychiatry related information on Cnr1

  • These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior [5].
  • We demonstrate here that young mice (6-7 weeks) with a genetic deletion of the cannabinoid CB1 receptor performed as well as WT mice, or often better, in a number of learning and memory paradigms, including animal models of skill-learning, partner recognition, and operant conditioning [6].
  • Mice without CB1 receptors are extremely hypoactive in a test for exploratory behavior (open-field test), showing markedly reduced locomotion and rearing [7].
  • CB1-/- mice exhibited dramatically reduced voluntary alcohol consumption, and completely lacked alcohol-induced DA release in the nucleus accumbens, as compared to wild-type mice [8].
  • In contrast, neither the increase in memory performance assessed by the object recognition test, nor the reduction of morphine withdrawal symptoms, showed age dependence in CB1 KO mice [9].

High impact information on Cnr1

  • Here we investigated whether activation of cannabinoid CB1 receptors (encoded by Cnr1) promotes progression of fibrosis [1].
  • Genetic or pharmacological inactivation of CB1 receptors decreased fibrogenesis by lowering hepatic transforming growth factor (TGF)-beta1 and reducing accumulation of fibrogenic cells in the liver after apoptosis and growth inhibition of hepatic myofibroblasts [1].
  • Pharmacological antagonists of CB1 and CB2 receptors prevented ovariectomy-induced bone loss in vivo and caused osteoclast inhibition in vitro by promoting osteoclast apoptosis and inhibiting production of several osteoclast survival factors [10].
  • Colocalization of CB1 and beta2-adrenergic receptors in the oviduct muscularis implies that a basal endocannabinoid tone in collaboration with adrenergic receptors coordinates oviductal motility for normal journey of embryos into the uterus [11].
  • In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents [12].

Chemical compound and disease context of Cnr1


Biological context of Cnr1


Anatomical context of Cnr1

  • Cannabinoid receptor type 1 (CB1) is widely distributed in neurons and nonneuronal cells in brain and peripheral organs including sperm, eggs, and preimplantation embryos [20].
  • Using CB1/2-/- murine embryonic fibroblasts, we present the first direct evidence that both cannabinoid receptors 1 and 2 (CB1/2) are involved in 2-AG-induced ERK activation [21].
  • We demonstrate that mRNA, receptor binding and function of CB2, but not CB1, receptors are dramatically and selectively up-regulated in spinal cords of G93A-SOD1 mice in a temporal pattern paralleling disease progression [22].
  • The endogenous cannabinoid anandamide is a lipid messenger activating cell growth via a cannabinoid receptor-independent pathway in hematopoietic cell lines [23].
  • These results indicate that CB1 receptors may promote antiinflammatory responses in astrocytes [24].

Associations of Cnr1 with chemical compounds


Physical interactions of Cnr1


Enzymatic interactions of Cnr1


Regulatory relationships of Cnr1


Other interactions of Cnr1

  • Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Delta(6)-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis [2].
  • Prior studies have demonstrated CB1 receptors (CB1Rs) and leptin modulation of cannabinoid synthesis in hypothalamic neurons [36].
  • Taken together, our data provide direct evidence suggesting that 2-AG may have a novel role in cell transformation and carcinogenesis in a signaling pathway involving CB1/2 and activation of Fyn, ERKs, and AP-1 [21].
  • Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB(1)), cannabinoid CB(2) receptor, and vanilloid receptor 1 (TRPV1) and the addition of the G(i) inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 muM THC but not by 10 muM THC [37].
  • In trying to detail functional interactions between CB1 and the CRH receptor type 1 (CRHR1), we performed double-label-in situ hybridisation on mouse forebrain sections to localise the transcripts encoding the two receptors at a cellular level [31].

Analytical, diagnostic and therapeutic context of Cnr1


  1. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Teixeira-Clerc, F., Julien, B., Grenard, P., Tran Van Nhieu, J., Deveaux, V., Li, L., Serriere-Lanneau, V., Ledent, C., Mallat, A., Lotersztajn, S. Nat. Med. (2006) [Pubmed]
  2. The endogenous cannabinoid system protects against colonic inflammation. Massa, F., Marsicano, G., Hermann, H., Cannich, A., Monory, K., Cravatt, B.F., Ferri, G.L., Sibaev, A., Storr, M., Lutz, B. J. Clin. Invest. (2004) [Pubmed]
  3. A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells. Davis, M.I., Ronesi, J., Lovinger, D.M. J. Biol. Chem. (2003) [Pubmed]
  4. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. Osei-Hyiaman, D., Liu, J., Zhou, L., Godlewski, G., Harvey-White, J., Jeong, W.I., Bátkai, S., Marsicano, G., Lutz, B., Buettner, C., Kunos, G. J. Clin. Invest. (2008) [Pubmed]
  5. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Ledent, C., Valverde, O., Cossu, G., Petitet, F., Aubert, J.F., Beslot, F., Böhme, G.A., Imperato, A., Pedrazzini, T., Roques, B.P., Vassart, G., Fratta, W., Parmentier, M. Science (1999) [Pubmed]
  6. Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Bilkei-Gorzo, A., Racz, I., Valverde, O., Otto, M., Michel, K., Sastre, M., Sarstre, M., Zimmer, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Altered gene expression in striatal projection neurons in CB1 cannabinoid receptor knockout mice. Steiner, H., Bonner, T.I., Zimmer, A.M., Kitai, S.T., Zimmer, A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. Hungund, B.L., Szakall, I., Adam, A., Basavarajappa, B.S., Vadasz, C. J. Neurochem. (2003) [Pubmed]
  9. Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: correlation with behaviour. Maccarrone, M., Valverde, O., Barbaccia, M.L., Castañé, A., Maldonado, R., Ledent, C., Parmentier, M., Finazzi-Agrò, A. Eur. J. Neurosci. (2002) [Pubmed]
  10. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Idris, A.I., van 't Hof, R.J., Greig, I.R., Ridge, S.A., Baker, D., Ross, R.A., Ralston, S.H. Nat. Med. (2005) [Pubmed]
  11. Aberrant cannabinoid signaling impairs oviductal transport of embryos. Wang, H., Guo, Y., Wang, D., Kingsley, P.J., Marnett, L.J., Das, S.K., DuBois, R.N., Dey, S.K. Nat. Med. (2004) [Pubmed]
  12. The endogenous cannabinoid system controls extinction of aversive memories. Marsicano, G., Wotjak, C.T., Azad, S.C., Bisogno, T., Rammes, G., Cascio, M.G., Hermann, H., Tang, J., Hofmann, C., Zieglgänsberger, W., Di Marzo, V., Lutz, B. Nature (2002) [Pubmed]
  13. Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in Oxazolone-Induced Contact Dermatitis in Mice. Oka, S., Wakui, J., Ikeda, S., Yanagimoto, S., Kishimoto, S., Gokoh, M., Nasui, M., Sugiura, T. J. Immunol. (2006) [Pubmed]
  14. Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Kimball, E.S., Schneider, C.R., Wallace, N.H., Hornby, P.J. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  15. Methanandamide increases COX-2 expression and tumor growth in murine lung cancer. Gardner, B., Zhu, L.X., Sharma, S., Tashkin, D.P., Dubinett, S.M. FASEB J. (2003) [Pubmed]
  16. Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase. Pacher, P., Bátkai, S., Osei-Hyiaman, D., Offertáler, L., Liu, J., Harvey-White, J., Brassai, A., Járai, Z., Cravatt, B.F., Kunos, G. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  17. Leptin-regulated endocannabinoids are involved in maintaining food intake. Di Marzo, V., Goparaju, S.K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G.I., Palmiter, R.D., Sugiura, T., Kunos, G. Nature (2001) [Pubmed]
  18. Regulation of gonadotropin-releasing hormone secretion by cannabinoids. Gammon, C.M., Freeman, G.M., Xie, W., Xie, W., Petersen, S.L., Wetsel, W.C. Endocrinology (2005) [Pubmed]
  19. Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Cobellis, G., Cacciola, G., Scarpa, D., Meccariello, R., Chianese, R., Franzoni, M.F., Mackie, K., Pierantoni, R., Fasano, S. Biol. Reprod. (2006) [Pubmed]
  20. Tuning the oviduct to the anandamide tone. Schuel, H. J. Clin. Invest. (2006) [Pubmed]
  21. 2-Arachidonoylglycerol stimulates activator protein-1-dependent transcriptional activity and enhances epidermal growth factor-induced cell transformation in JB6 P+ cells. Zhao, Q., He, Z., Chen, N., Cho, Y.Y., Zhu, F., Lu, C., Ma, W.Y., Bode, A.M., Dong, Z. J. Biol. Chem. (2005) [Pubmed]
  22. The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. Shoemaker, J.L., Seely, K.A., Reed, R.L., Crow, J.P., Prather, P.L. J. Neurochem. (2007) [Pubmed]
  23. The endogenous cannabinoid anandamide is a lipid messenger activating cell growth via a cannabinoid receptor-independent pathway in hematopoietic cell lines. Derocq, J.M., Bouaboula, M., Marchand, J., Rinaldi-Carmona, M., Ségui, M., Casellas, P. FEBS Lett. (1998) [Pubmed]
  24. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures. Molina-Holgado, F., Molina-Holgado, E., Guaza, C., Rothwell, N.J. J. Neurosci. Res. (2002) [Pubmed]
  25. Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia. Lichtman, A.H., Shelton, C.C., Advani, T., Cravatt, B.F. Pain (2004) [Pubmed]
  26. Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Jeong, W.I., Osei-Hyiaman, D., Park, O., Liu, J., Bátkai, S., Mukhopadhyay, P., Horiguchi, N., Harvey-White, J., Marsicano, G., Lutz, B., Gao, B., Kunos, G. Cell Metab. (2008) [Pubmed]
  27. Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake. Ortega-Gutiérrez, S., Hawkins, E.G., Viso, A., López-Rodríguez, M.L., Cravatt, B.F. Biochemistry (2004) [Pubmed]
  28. Differential G protein-coupled cannabinoid receptor signaling by anandamide directs blastocyst activation for implantation. Wang, H., Matsumoto, H., Guo, Y., Paria, B.C., Roberts, R.L., Dey, S.K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Cannabinoid receptors and their endogenous agonists. Felder, C.C., Glass, M. Annu. Rev. Pharmacol. Toxicol. (1998) [Pubmed]
  30. Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. Bisogno, T., Melck, D., De Petrocellis, L., Bobrov MYu, n.u.l.l., Gretskaya, N.M., Bezuglov, V.V., Sitachitta, N., Gerwick, W.H., Di Marzo, V. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  31. Coexpression of the cannabinoid receptor type 1 with the corticotropin-releasing hormone receptor type 1 in distinct regions of the adult mouse forebrain. Hermann, H., Lutz, B. Neurosci. Lett. (2005) [Pubmed]
  32. 2-Arachidonoyl-glycerol suppresses interferon-gamma production in phorbol ester/ionomycin-activated mouse splenocytes independent of CB1 or CB2. Kaplan, B.L., Ouyang, Y., Rockwell, C.E., Rao, G.K., Kaminski, N.E. J. Leukoc. Biol. (2005) [Pubmed]
  33. Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus. Derkinderen, P., Ledent, C., Parmentier, M., Girault, J.A. J. Neurochem. (2001) [Pubmed]
  34. Comparative analysis of fatty acid amide hydrolase and cb(1) cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling. Egertová, M., Cravatt, B.F., Elphick, M.R. Neuroscience (2003) [Pubmed]
  35. Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. McCoy, K.L., Matveyeva, M., Carlisle, S.J., Cabral, G.A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  36. Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Jo, Y.H., Chen, Y.J., Chua, S.C., Talmage, D.A., Role, L.W. Neuron (2005) [Pubmed]
  37. Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila. Lu, T., Newton, C., Perkins, I., Friedman, H., Klein, T.W. Eur. J. Pharmacol. (2006) [Pubmed]
  38. Corticotropin-releasing hormone-mediated induction of intracellular signaling pathways and brain-derived neurotrophic factor expression is inhibited by the activation of the endocannabinoid system. Bayatti, N., Hermann, H., Lutz, B., Behl, C. Endocrinology (2005) [Pubmed]
  39. Endocannabinoids as physiological regulators of colonic propulsion in mice. Pinto, L., Izzo, A.A., Cascio, M.G., Bisogno, T., Hospodar-Scott, K., Brown, D.R., Mascolo, N., Di Marzo, V., Capasso, F. Gastroenterology (2002) [Pubmed]
  40. The preimplantation mouse embryo is a target for cannabinoid ligand-receptor signaling. Paria, B.C., Das, S.K., Dey, S.K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  41. Behaviroal, pharmacological, and molecular characterization of an amphibian cannabinoid receptor. Soderstrom, K., Leid, M., Moore, F.L., Murray, T.F. J. Neurochem. (2000) [Pubmed]
WikiGenes - Universities