Cannabinoid receptors are a class of cell receptors belonging to the superfamily of G-protein-bound membrane receptors [1] [2] . Cannabinoid receptors have three types of ligands:
- endocannabinoids ( anandamide and 2-arachidonoylglycerol ), which are formed mainly in the mastoid bodies of the limbic system of the brain;
- phytocannabinoids ( THC and some other compounds);
- synthetic cannabinoids ( HU-210 ).
Content
- 1 Discovery History
- 2 Types of cannabinoid receptors and their localization
- 3 Ligands and effects
- 3.1 The affinity (affinity) and selectivity (selectivity) of binding of cannabinoids to receptors
- 4 notes
- 5 Links
Discovery History
First identified in 1988 by a team of researchers from St. Louis University Medical School, USA using tritium- labeled synthetic cannabinoid CP-55,940 in rat brain, with only one type of CP-55,940 binding site observed and competitive binding of CP-55,940 and Δ-9-tetrahydrocannabinol observed [3]
Types of cannabinoid receptors and their localization
Currently, two types of mammalian cannabinoid receptors are well studied: CB 1 and CB 2 . [4] [5]
The CB 1 receptor is expressed mainly in the central and peripheral nervous system , but also in the lungs , kidneys and liver . CB 1 receptor concentration is observed in the central nervous system ( cerebral cortex , hippocampus , cerebellum , caudate nucleus of the striatum , reticular part of the substantia nigra ). CB 1 receptors in significantly lower concentrations are also present in the peripheral nervous system, including the peripheral ganglia, pituitary, adrenal glands, and heart.
CB 2 receptors were first detected in the spleen , then in other glandular tissues ( pancreas , ovaries , etc.) CB 2 receptor is mainly expressed in immunocompetent and hematopoietic cells. [6]
There is evidence of the existence of new cannabinoid receptors [7] . It is suggested that a new class of cannabinoid receptors can be expressed in endothelial cells and in the central nervous system. In 2007, the binding of a number of cannabinoids to the G-protein-bound membrane receptor GPR55 located in the brain was described. [8]
The amino acid sequence of CB 1 and CB 2 receptors have about 44% similarity. [9] [10] If only the transmembrane regions of the receptors are compared, the amino acid similarity of the receptors will be approximately 68%. [2] Cannabinoids bind to receptors stereoselectively . Selective synthetic cannabinoids have been developed that can theoretically be useful in the treatment of certain diseases, in particular, obesity and other metabolic disorders. [eleven]
Cannabinoid receptors are thought to be unique to the Chordata type. Although enzymes involved in the biosynthesis and inactivation of endocannabinoids, as well as proteins involved in endocannabinoid signaling (including CB 1/2 receptor targets), are widespread among animals. [12]
Ligands and effects
In a natural state, these receptors are activated by anandamides and contribute to the inhibition of hyperactivity caused by an excess of dopamine . introduction of exogenous cannabinoids (for example, tetrahydrocannabinol ) into the body affects CB 1 in a similar way, but much more intensively. Unlike CB 1 , CB 2 receptors bind exogenous cannabinoids well, but exhibit low affinity for anandamides.
Affinity (affinity) and selectivity (selectivity) of receptor binding of cannabinoids
| Affinity for CB 1 (K i ) | Efficiency to CB 1 | Affinity for CB 2 (K i ) | Efficiency to CB 2 | Type of | References | |
|---|---|---|---|---|---|---|
| Anandamide | 78 nM | Full agonist | 370 nM | ? | Endogenous | |
| ? | Agonist | ? | ? | Endogenous | ||
| ? | Full agonist | ? | ? | Endogenous | ||
| 21 nM | Full agonist | 480 nM | Full agonist | Endogenous | ||
| Δ-9-Tetrahydrocannabinol | 10 nM | Partial agonist | 24 nM | Partial agonist | Phytogenic | [13] [13] |
| Epigallocatechin Gallate (EGCG) | 33.6 μM | Agonist | > 50 μM | ? | Phytogenic | |
| 0.72 μM | ? | > 10 μM | ? | Phytogenic | [fourteen] | |
| 52.3 nM | Agonist | 0.28 nM | Agonist | Synthetic | [fifteen] | |
| 1.5 nM | Agonist | 20.4 nM | Agonist | Synthetic | [16] | |
| 0.28 nM | Agonist | 1.48 nM | Agonist | Synthetic | [16] | |
| 150 nM | Agonist | 1.8 nM | Full agonist | Synthetic | [17] | |
| 9.0 nM | Agonist | 2.94 nM | Agonist | Synthetic | [eighteen] | |
| 383 nM | Agonist | 13.8 nM | Agonist | Synthetic | [eighteen] | |
| JWH-018 | 9.00 ± 5.00 nM | Full agonist | 2.94 ± 2.65 nM | Full agonist | Synthetic |
Notes
- ↑ Howlett AC The cannabinoid receptors // Prostaglandins & Other Lipid Mediators. - 2002 .-- 1 August ( vol. 68-69 ). - P. 619-631 . - ISSN 1098-8823 . - DOI : 10.1016 / S0090-6980 (02) 00060-6 . - PMID 12432948 .
- ↑ 1 2 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 .
- ↑ Devane WA et al. Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology, 1988 Nov; 34 (5): 605-13.
- ↑ Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990). "Structure of a cannabinoid receptor and functional expression of the cloned cDNA." Nature . 346 (6284): 561-4. doi : 10.1038 / 346561a0 . PMID 2165569 .
- ↑ Gérard CM, Mollereau C, Vassart G, Parmentier M (1991). "Molecular cloning of a human cannabinoid receptor which is also expressed in testis . " Biochem. J. 279 (Pt 1): 129–34. doi : 10.1042 / bj2790129 . PMC . PMID 1718258 .
- ↑ Pacher P., Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? (Eng.) // Prog Lipid Res. : journal. - 2011. - Vol. 50 , no. 2 . - P. 193-211 . - DOI : 10.1016 / j.plipres.2011.01.001 . - PMID 21295074 .
- ↑ Begg M, Pacher P, Batkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G (2005). "Evidence for novel cannabinoid receptors." Pharmacol Ther . 106 (2): 133–45. doi : 10.1016 / j.pharmthera.2004.11.00.00 . PMID 15866316 .
- ↑ Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007). "The orphan receptor GPR55 is a novel cannabinoid receptor . " Br. J. Pharmacol . 152 (7): 1092–1101. doi : 10.1038 / sj.bjp.0707460 . PMC . PMID 17876302 .
- ↑ D; Latek; Kolinski, M; Ghoshdastider, U; Debinski, A; Bombolewski, R; Plazinska, A; Jozwiak, K; Filipek, S. Modeling of ligand binding to G protein coupled receptors: Cannabinoid CB1, CB2 and adrenergic β 2 AR (Eng.) // Journal of Molecular Modeling: journal. - 2011. - Vol. 17 , no. 9 . - P. 2353-2366 . - DOI : 10.1007 / s00894-011-0986-7 . - PMID 21365223 .
- ↑ Munro S, Thomas KL, Abu-Shaar M (1993). "Molecular characterization of a peripheral receptor for cannabinoids." Nature . 365 (6441): 61–65. doi : 10.1038 / 365061a0 . PMID 7689702 .
- ↑ Kyrou I., Valsamakis G., Tsigos C. The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome (Eng.) // Ann. NY Acad. Sci. : journal. - 2006 .-- November ( vol. 1083 ). - P. 270-305 . - DOI : 10.1196 / annals.1367.024 . - PMID 17148745 .
- ↑ Maurice R. Elphick (2012), " The evolution and comparative neurobiology of endocannabinoid signalling ", Philosophical Transactions of the Royal Society of London B T. 367 (1607): 3201–3215 , DOI 10.1098 / rstb.2011.0394
- ↑ 1 2 PDSP Database - UNC . Date of treatment June 11, 2013. Archived on November 8, 2013.
- ↑ Ligresti, A .; Villano, R .; Allarà, M .; Ujváry, IN; Di Marzo, V. Kavalactones and the endocannabinoid system: The plant-derived yangonin is a novel CB1 receptor ligand (English) // Pharmacological Research : journal. - 2012. - Vol. 66 , no. 2 . - P. 163-169 . - DOI : 10.1016 / j.phrs.2012.04.003 . - PMID 22525682 .
- ↑ Template: Ref patent2
- ↑ 1 2 Template: Ref patent2
- ↑ 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 Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB (2) cannabinoid receptor activity (Eng.) // J. Med. Chem. : journal. - 2010 .-- January ( vol. 53 , no. 1 ). - P. 295-315 . - DOI : 10.1021 / jm901214q . - PMID 19921781 .
- ↑ 1 2 Aung MM, Griffin G., Huffman JW, Wu M., Keel C., Yang B., Showalter VM, Abood ME, Martin BR Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB 1 and CB 2 receptor binding (Eng.) // Drug Alcohol Depend: journal. - 2000 .-- August ( vol. 60 , no. 2 ). - P. 133-140 . - DOI : 10.1016 / S0376-8716 (99) 00152-0 . - PMID 10940540 .
Links
- Nycall R., Alger B. Marijuana Brain, or The New Signaling System