Cannabinoid receptor 2

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Cannabinoid receptor 2
Cannabinoid receptor 2
Helix 6 of the human CNR2

Existing structural data: 2KI9

Properties of human protein
Mass / length primary structure 360 amino acids
Identifier
Gene names CNR2 , CB2A, CB2B
External IDs
Occurrence
Homology family Cannabinoid receptors

The cannabinoid receptor 2 (or officially short: CNR2 , or alternative abbreviated designation: CB2 , CX5 , CB-2 ) mediates the effects of endogenous cannabinoids as well as exogenously supplied cannabinoids such. B. Δ 9 - Tetrahydrocannabinol from Cannabis sativa in cells of the immune system and cells that are involved in bone formation ( osteoblasts ) and bone breakdown ( osteoclasts ), and is therefore part of the endocannabinoid system .

genetics

The cannabinoid receptor 2 is encoded by a gene on chromosome 1p36.11 and belongs to the G-protein-coupled receptor family. It is transcribed into a 360 amino acid protein .

Functions

CB2 receptors have been detected in the central nervous system of various animal species and the fact that their expression is increased by inflammatory stimuli suggests that they are involved in the pathogenesis and endogenous response to neuronal injury.

Effect on Alzheimer's disease

CB2 activation could have positive effects on the progression of Alzheimer's disease through various mechanisms , including a reduction in local, microglia- mediated inflammation and an increased beta-amyloid removal rate.

Effect in HIV-associated encephalitis

CB2 receptors may be involved in the inflammatory response to viral infection of the brain by modulating the production of inflammatory molecules and the entry of peripheral cells into the central nervous system.

Ligands

CB 1 - affinity (K i ) CB 1 effect CB 2 affinity (K i ) CB 2 effect Occurrence / origin source
Anandamide 78 nM Full agonist 370 nM Partial agonist endogenous, quadruple unsaturated fatty acid
2-arachidonylglycerol (2-AG) 58.3 or 470 nM Full agonist 145 nM Full agonist endogenous
2-arachidonyl glyceryl ether (2-AGE, noladin ether) 21 nM Full agonist 480 nM Full agonist endogenous -
HU-210 0.41 nM Full agonist - - exogenous , synthetic
AM-1221 52.3 nM Agonist 0.28 nM Agonist exogenous, synthetic
AM-1235 1.5 nM Agonist 20.4 nM Agonist exogenous, synthetic
AM-2232 0.28 nM Agonist 1.48 nM Agonist exogenous, synthetic
AM-2201 1.0 nM Full agonist - - exogenous, synthetic
JWH-007 9.0 nM Agonist 2.94 nM Agonist exogenous, synthetic
JWH-015 383 nM Agonist 13.8 nM Agonist exogenous, synthetic
JWH-018 9.0 ± 5.0 nM Full agonist 2.94 ± 2.65 nM Full agonist exogenous, synthetic
JWH-019 - Agonist - - exogenous, synthetic -
JWH-073 8.9 nM Partial agonist - - exogenous, synthetic
JWH-122 0.69 nM Full agonist - - exogenous, synthetic
CP-47,497 2.1 nM Agonist - - exogenous, synthetic
CP-55,940 2.6 nM Agonist - - exogenous, synthetic
Δ 9 - tetrahydrocannabinol 10 nM Partial agonist 24 nM Partial agonist exogenous, hemp plant (cannabis)
Cannabidiol - Agonist / antagonist - - exogenous, hemp plant
Yangonin 720 nM Agonist - - exogenous, kava plant (Piper methysticum)
(-) - Epigallocatechin-3-O-gallate (EGCG) 33.6 µM Agonist > 50 μM ? exogenous, tea plant (Camellia sinensis)
(-) - Epigallocatechin (EGC) 35.7 µM Agonist - - exogenous, tea plant
(-) - Epicatechin-3-O-gallate (ECG) 47.3 µM Agonist - - exogenous, tea plant
Rimonabant - antagonist - - exogenous, synthetic
Ibipinabant (SLV319, BMS-646,256) - antagonist - -
Otenabant (CP-945,598) - antagonist - -
Pregnenolone - antagonist - - endogenous, prohormone of progesterone
Δ8- tetrahydrocannabivarin - antagonist - -
Cannabigerol - antagonist - -
Virodhamin - antagonist - -
UR-144 150 nM Full agonist 1.8 nM Full agonist exogenous, synthetic
N-arachidonoyl dopamine (NADA) 250 nM Agonist 12 µM ? endogenous

See also

Web links

Individual evidence

  1. ↑ CNR2. Free Dictionary, 2012, accessed December 12, 2015 .
  2. ↑ a b c C. Benito, RM Tolón, MR Pazos, E. Núñez, AI Castillo, J. Romero: Cannabinoid CB2 receptors in human brain inflammation. In: British journal of pharmacology. Volume 153, Number 2, January 2008, pp. 277-285, doi: 10.1038 / sj.bjp.0707505 , PMID 17934510 , PMC 2219537 (free full text) (review).
  3. ↑ a b c C. C. Felder, KE Joyce, EM Briley et al. : Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors . In: Mol Pharmacol . 48, No. 3, September 1995, pp. 443-50. PMID 7565624 .
  4. ↑ a b C. S. Breivogel, G. Griffin, V. Di Marzo, BR Martin: Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. In: Molecular pharmacology. Volume 60, Number 1, July 2001, ISSN  0026-895X , pp. 155-163, PMID 11408610 .
  5. ↑ a b R.G. Pertwee et al. : International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB 1 and CB 2 . In: Pharmacological Reviews . 62, No. 4, December 2010, pp. 588-631. doi : 10.1124 / pr.110.003004 . PMID 21079038 .
  6. ↑ F. Mauler, J. Mittendorf, E. Horváth, J. De Vry: Characterization of the diarylether sulfonylester (-) - (R) -3- (2-hydroxymethylindanyl-4-oxy) phenyl-4,4,4- trifluoro-1-sulfonate (BAY 38-7271) as a potent cannabinoid receptor agonist with neuroprotective properties. In: Journal of Pharmacology and Experimental Therapeutics . Volume 302, Number 1, July 2002, ISSN  0022-3565 , pp. 359-368, PMID 12065738 .
  7. ↑ a b Patent WO200128557 : Cannabimimetic indole derivatives. Published July 7, 2001 , Inventors: A. Makriyannis, H. Deng. ‌
  8. ↑ a b Patent US7241799 : Cannabimimetic indole derivatives. Published October 10, 2007 , Inventors: A. Makriyannis, H. Deng. ‌
  9. ↑ a b M. M. Aung, G. Griffin, JW Huffman, M. Wu, C. Keel, B. Yang, VM Showalter, ME Abood, BR Martin: Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB (1 ) and CB (2) receptor binding. In: Drug and alcohol dependence. Volume 60, Number 2, August 2000, ISSN  0376-8716 , pp. 133-140, PMID 10940540 .
  10. ↑ Mie Mie Aung, Graeme Griffin and others. a .: Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. In: Drug and Alcohol Dependence. 60, 2000, p. 133, doi: 10.1016 / S0376-8716 (99) 00152-0 .
  11. ↑ JW Huffman, G. Zengin, MJ Wu, J. Lu, G. Hynd, K. Bushell, AL Thompson, S. Bushell, C. Tartal, DP Hurst, PH Reggio, DE Selley, MP Cassidy, JL Wiley, BR Martin: Structure-activity relationships for 1-alkyl-3- (1-naphthoyl) indoles at the cannabinoid CB (1) and CB (2) receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB (2) receptor agonists. In: Bioorganic & Medicinal Chemistry . Volume 13, Number 1, January 2005, ISSN  0968-0896 , pp. 89-112, doi: 10.1016 / j.bmc.2004.09.050 , PMID 15582455 .
  12. ↑ JY Shim, WJ Welsh, AC Howlett: Homology model of the CB1 cannabinoid receptor: sites critical for nonclassical cannabinoid agonist interaction . In: Biopolymers , 71, No. 2, 2003, pp. 169-189; PMID 12767117 .
  13. ↑ Roger Pertwee. Cannabinoids. Handbook of Experimental Pharmacology Volume 168. Springer. ISBN 3-540-22565-X .
  14. ^ PJ Little, DR Compton, MR Johnson, LS Melvin, BR Martin: Pharmacology and stereoselectivity of structurally novel cannabinoids in mice . In: Journal of Pharmacology and Experimental Therapeutics , 1988, 247 , pp. 1046-1051.
  15. ↑ PDSP Database - UNC . Archived from the original on November 8, 2013. Info: The archive link was automatically inserted and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved June 11, 2013. @1@ 2Template: Webachiv / IABot / pdsp.med.unc.edu
  16. Jump up ↑ A. Thomas, GL Baillie, AM Phillips, RK Razdan, RA Ross, RG Pertwee: Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. In: British Journal of Pharmacology . Volume 150, Number 5, March 2007, ISSN  0007-1188 , pp. 613-623, doi: 10.1038 / sj.bjp.0707133 , PMID 17245363 , PMC 2189767 (free full text).
  17. ↑ A. Ligresti, R. Villano, M. Allarà, I. Ujváry, V. Di Marzo: Kavalactones and the endocannabinoid system: the plant-derived yangonin is a novel CB1 receptor ligand. In: Pharmacological Research . Volume 66, Number 2, August 2012, ISSN  1096-1186 , pp. 163-169, doi: 10.1016 / j.phrs.2012.04.003 , PMID 22525682 .
  18. ↑ a b c G. Korte, A. Dreiseitel, P. Schreier, A. Oehme, S. Locher, S. Geiger, J. Heilmann, PG Sand: Tea catechins' affinity for human cannabinoid receptors. In: Phytomedicine . Volume 17, number 1, January 2010, ISSN  1618-095X , pp. 19-22, doi: 10.1016 / j.phymed.2009.10.001 , PMID 19897346 .
  19. ↑ JH Lange, HK Coolen u. a .: Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB (1) cannabinoid receptor antagonists. In: Journal of medicinal chemistry. Volume 47, Number 3, January 2004, ISSN  0022-2623 , pp. 627-643, doi: 10.1021 / jm031019q , PMID 14736243 .
  20. ↑ Min-ah Kim, Hoseop Yun, HyunJung Kwak, Jeongmin Kim, Jinhwa Lee: Design, chemical synthesis, and biological evaluation of novel triazolyl analogues of taranabant (MK-0364), a cannabinoid-1 receptor inverse agonist. In: Tetrahedron. 64, 2008, pp. 10802-10809, doi: 10.1016 / j.tet.2008.09.057 .
  21. ^ RG Pertwee, A. Thomas, LA Stevenson, RA Ross, SA Varvel, AH Lichtman, BR Martin, RK Razdan: The psychoactive plant cannabinoid, Δ9-tetrahydrocannabinol, is antagonized by Δ8- and Δ9-tetrahydrocannabivarin in mice in vivo. In: British Journal of Pharmacology. 150, 2007, pp. 586-594, doi: 10.1038 / sj.bjp.0707124 .
  22. ↑ MG Cascio, LA Gauson u. a .: Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. In: British journal of pharmacology. Volume 159, number 1, January 2010, ISSN  1476-5381 , pp. 129-141, doi: 10.1111 / j.1476-5381.2009.00515.x , PMID 20002104 , PMC 2823359 (free full text).
  23. ↑ AC Porter, JM Sauer et al. a .: Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. In: The Journal of pharmacology and experimental therapeutics. Volume 301, Number 3, June 2002, ISSN  0022-3565 , pp. 1020-1024, PMID 12023533 .
  24. ↑ JM Frost, MJ Dart, KR Tietje, TR Garrison, GK Grayson, AV Daza, OF El-Kouhen, BB Yao, GC Hsieh, M. Pai, CZ Zhu, P. Chandran, MD Meyer: Indol-3-ylcycloalkyl ketones : effects of N1 substituted indole side chain variations on CB (2) cannabinoid receptor activity . In: Journal of Medicinal Chemistry . 53, No. 1, January 2010, pp. 295-315. doi : 10.1021 / jm901214q . PMID 19921781 .