Kanabinoidni receptor 2

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Kanabinoidni receptor 2 (makrofag)

Prikaz baziran na PDB 2KI9.
Dostupne strukture
2KI9
Identifikatori
SimboliCNR2; CB-2; CB2; CX5
Vanjski IDOMIM: 605051 MGI: 104650 HomoloGene: 1389 IUPHAR: CB2 GeneCards: CNR2 Gene
Ontologija gena
Molekularna funkcija • aktivnost kanabinoidnog receptora
Celularna komponenta • ćelijska membrana
• integralno sa ćelijskom membranom
• sinaptozom
• dendrit
Biološki proces • respons na amfetamin
• inflamatorni respons
• imunski respons
• signalni put G-protein spregnutog receptora, spregnut sa cikličnim nukleotidnim sekundarnim glasnikom
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez126912802
EnsemblENSG00000188822ENSMUSG00000062585
UniProtP34972P47936
RefSeq (mRNA)NM_001841.2NM_009924.3
RefSeq (protein)NP_001832.1NP_034054.3
Lokacija (UCSC)Chr 1:
24.2 - 24.29 Mb		Chr 4:
135.45 - 135.48 Mb
PubMed pretraga[1][2]

Kanabinoidni receptor tip 2 (CB2) je G protein spregnuti receptor iz familije kanabinoidnih receptora koja je kod ljudi kodirana CNR2 genom.[1][2] On je blisko srodan sa kanabinoidnim receptorom tip 1, koji je u znatnoj meri odgovoran za efikasnost endokanabinoidno posredovane presinaptičke inhibicije, psihoaktivnih svojstava tetrahidrokanabinola, aktivnog agenta marihuane, i drugih fitokanabinoida.[1][3] Glavni endogeni ligand za CB2 receptor je 2-arahidonoilglicerol (2-AG).[2]

CB2 je bio kloniran 1993. od strane istraživačke grupe iz Kembridža koja je tragala za drugim kanabinoidnim receptorom koji bi mogla da objasni farmakološke osobine tetrahidrokanabinola.[1] Receptor je identifikovan među cDNA molekulima na bazi sličnosti njegove aminokiselinske sekvence sa kanabinoidnim receptorskim tipom 1 (CB1) receptora, otkrivenim 1990.[4] Otkriće ovog receptora je pomoglo u pružanju molekulskog objašnjenja za uspostavljanje dejstva kanabinoida u imunskom sistemu.

Struktura

CB2 receptor je kodiran CNR2 genom.[5][6] Oko 360 aminokiselina sačinjavaju ljudski CB2 receptor, te je on donekle kraći od 473 aminokiselina dugog CB1 receptora.[6]

Kao i drugi G protein spregnutih receptor, the CB2 receptor ima sedam transmembranskih domena,[7] glikozilisani N-terminus, i intraćelijski C-terminus.[6] C-terminus CB2 receptora ima kritičnu ulogu u regulaciji ligandom indukovane desenzitizacije receptora i umanjenom izražavanju nakon višestruke primene agonista,[6] te je moguće da čini receptor manje responzivnim na specifične ligande.

Ljudski CB1 i CB2 receptori imaju oko 44% aminokiselinske sličnosti.[1] Kad se samo transmembranski regioni receptora uzmu u obzir, aminokiselinska sličnost između dva receptora je oko 68%.[6] Aminokiselinska sekvenca CB2 receptora je u manjoj meri očuvana kod različitih vrsta (čovek i glodari) u poređenju sa CB1 receptorom.[8] Na osnovu računarskog modelovanja, interakcija liganda sa CB2 receptorskim ostacima S3.31 i F5.46 određuje razliku selektivnosti između CB1 i CB2 receptora.[9] U CB2 receptorima, lipofilne grupe formiraju interakcije sa F5.46 ostatkom, omogućavajući formiranje vodonične veze sa S3.31 ostatkom.[9] Te interakcije indukuju konformacionu promenu strukture receptora, koja inicira aktivaciju raznih intraćelijskih signalnih puteva.[9]

Ligandi

Dostupan je znatan broj selektivnih liganda CB2 receptora.[10]

Agonisti

Antagonisti i inverzni agonisti

Reference

  1. ↑ 1,0 1,1 1,2 1,3 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. 
  2. ↑ 2,0 2,1 Basu, S.; Ray, A.; Dittel, B. N. (2011). „Cannabinoid Receptor 2 (CB2) is Critical for the Homing and Retention of Marginal Zone B Lineage Cells and for Efficient T-independent Immune Responses”. The Journal of Immunology 187 (11): 5720–5732. DOI:10.4049/jimmunol.1102195. PMC 3226756. PMID 22048769. 
  3. ↑ „Entrez Gene: CNR2 cannabinoid receptor 2 (macrophage)”. 
  4. ↑ Elphick, M. R.; Egertova, M. (2001). „The neurobiology and evolution of cannabinoid signalling”. Philosophical Transactions of the Royal Society B: Biological Sciences 356 (1407): 381–408. DOI:10.1098/rstb.2000.0787. PMC 1088434. PMID 11316486. 
  5. ↑ Munro S, Thomas KL, Abu-Shaar M (1993). „Molecular characterization of a peripheral receptor for cannabinoids”. Nature 365 (6441): 61–5. DOI:10.1038/365061a0. PMID 7689702. 
  6. ↑ 6,0 6,1 6,2 6,3 6,4 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. 
  7. ↑ 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. 
  8. ↑ 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. 
  9. ↑ 9,0 9,1 9,2 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. 
  10. ↑ 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. Arhivirano iz originala na datum 2013-01-12. Pristupljeno 2014-05-04. 

Literatura

  • Oddi S, Spagnuolo P, Bari M, et al. (2007). „Differential modulation of type 1 and type 2 cannabinoid receptors along the neuroimmune axis. Differential Modulation of Type 1 and Type 2 Cannabinoid Receptors along the Neuroimmune Axis”. Int. Rev. Neurobiol.. International Review of Neurobiology 82: 327–37. DOI:10.1016/S0074-7742(07)82017-4. ISBN 978-0-12-373989-6. PMID 17678969. 
  • Galiègue S, Mary S, Marchand J, et al. (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. 
  • Munro S, Thomas KL, Abu-Shaar M (1993). „Molecular characterization of a peripheral receptor for cannabinoids”. Nature 365 (6441): 61–5. DOI:10.1038/365061a0. PMID 7689702. 
  • Shire D, Calandra B, Rinaldi-Carmona M, et al. (1996). „Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor”. Biochim. Biophys. Acta 1307 (2): 132–6. DOI:10.1016/0167-4781(96)00047-4. PMID 8679694. 
  • Tao Q, McAllister SD, Andreassi J, et al. (1999). „Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity”. Mol. Pharmacol. 55 (3): 605–13. PMID 10051546. 
  • Nong L, Newton C, Friedman H, Klein TW (2002). „CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types”. Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 493: 229–33. DOI:10.1007/0-306-47611-8_27. ISBN 0-306-46466-7. PMID 11727770. 
  • Ho BY, Current L, Drewett JG (2002). „Role of intracellular loops of cannabinoid CB(1) receptor in functional interaction with G(alpha16)”. FEBS Lett. 522 (1–3): 130–4. DOI:10.1016/S0014-5793(02)02917-4. PMID 12095632. 
  • Matias I, Pochard P, Orlando P, et al. (2002). „Presence and regulation of the endocannabinoid system in human dendritic cells”. Eur. J. Biochem. 269 (15): 3771–8. DOI:10.1046/j.1432-1033.2002.03078.x. PMID 12153574. 
  • Song ZH, Feng W (2002). „Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function”. FEBS Lett. 531 (2): 290–4. DOI:10.1016/S0014-5793(02)03537-8. PMID 12417328. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Casanova ML, Blázquez C, Martínez-Palacio J, et al. (2003). „Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors”. J. Clin. Invest. 111 (1): 43–50. DOI:10.1172/JCI16116. PMC 151833. PMID 12511587. 
  • Feng W, Song ZH (2003). „Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor”. Biochem. Pharmacol. 65 (7): 1077–85. DOI:10.1016/S0006-2952(03)00005-4. PMID 12663043. 
  • Kishimoto S, Gokoh M, Oka S, et al. (2003). „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”. J. Biol. Chem. 278 (27): 24469–75. DOI:10.1074/jbc.M301359200. PMID 12711605. 
  • Jorda MA, Rayman N, Valk P, et al. (2003). „Identification, characterization, and function of a novel oncogene: the peripheral cannabinoid receptor Cb2”. Ann. N. Y. Acad. Sci. 996: 10–6. DOI:10.1111/j.1749-6632.2003.tb03227.x. PMID 12799277. 
  • Rayman N, Lam KH, Laman JD, et al. (2004). „Distinct expression profiles of the peripheral cannabinoid receptor in lymphoid tissues depending on receptor activation status”. J. Immunol. 172 (4): 2111–7. PMID 14764676. 
  • Rao GK, Zhang W, Kaminski NE (2004). „Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells”. J. Leukoc. Biol. 75 (5): 884–92. DOI:10.1189/jlb.1203638. PMID 14966196. 
  • Alberich Jordà M, Rayman N, Tas M, et al. (2004). „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”. Blood 104 (2): 526–34. DOI:10.1182/blood-2003-12-4357. PMID 15039279. 
  • Núñez E, Benito C, Pazos MR, et al. (2004). „Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study”. Synapse 53 (4): 208–13. DOI:10.1002/syn.20050. PMID 15266552. 
  • Gokoh M, Kishimoto S, Oka S, et al. (2005). „2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells”. Biochem. J. 386 (Pt 3): 583–9. DOI:10.1042/BJ20041163. PMC 1134878. PMID 15456404. 
  • Miller, A. M.; Stella, N. (2008). „CB2receptor-mediated migration of immune cells: it can go either way”. British Journal of Pharmacology 153 (2): 299. DOI:10.1038/sj.bjp.0707523. PMC 2219538. PMID 17982478. 

Vidi još

Spoljašnje veze

  • „Cannabinoid Receptors: CB2”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2012-03-05. Pristupljeno 2014-05-04. 
  • p
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Klasa A: Rodopsinu slični
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat  • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6)  • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)