Wikipedia

CNR1

Kanabinoidni receptor tipa 1 (CB1), znan i kao kanabinoid receptor 1, jest G protein-spregnuti kanabinoidni receptor koji je kod ljudi kodiran genom CNR1.[5] Ljudski CB1 receptor je eksprimiran u perifernom i centralnom nervnom sistemu. Aktivira se pomoću: endokanabinoida, grupe retrogradnih neurotransmitera koji uključuju anandamid i 2-arahidonoilglicerol (2-AG), biljni fitokanabinoid, kao što je spoj THC, koji je aktivni sastojak psihoaktivne droge kanabisa i, sintetski analozi THC-a. CB1 je antagoniziran pomoću fitokanabinoida tetrahidrokanabivarina (THCV).[6][7]

CNR1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1LVQ, 1LVR, 2B0Y, 2KOE, 2MZ3, 2MZ2, 2MZA,%%s1LVQ, 1LVR, 2B0Y, 2KOE

Identifikatori
AliasiCNR1
Vanjski ID-jeviOMIM: 114610 MGI: 104615 HomoloGene: 7273 GeneCards: CNR1
Lokacija gena (čovjek)
Hromosom 6 (čovjek)
Hrom.Hromosom 6 (čovjek)[1]
Hromosom 6 (čovjek)
Genomska lokacija za CNR1
Genomska lokacija za CNR1
Bend6q15Početak88,139,864 bp[1]
Kraj88,166,347 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za CNR1
Genomska lokacija za CNR1
Bend4 A5|4 16.28 cMPočetak33,924,593 bp[2]
Kraj33,948,831 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• G protein-coupled receptor activity
• signal transducer activity
• cannabinoid receptor activity
• GO:0001948, GO:0016582 vezivanje za proteine
• voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels
Ćelijska komponenta• integral component of membrane
• intracellular membrane-bounded organelle
• membrana
• growth cone
• integral component of plasma membrane
• Akson
• Lipidni splav
• ćelijska membrana
• presynaptic membrane
• mitohondrija
• mitochondrial outer membrane
• projekcija ćelije
• integral component of mitochondrial membrane
• presynapse
• glutamatergic synapse
• GABA-ergic synapse
• integral component of presynaptic membrane
Biološki proces• negative regulation of nitric-oxide synthase activity
• negative regulation of mast cell activation
• glucose homeostasis
• response to nutrient
• regulation of insulin secretion
• negative regulation of blood pressure
• adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• maternal process involved in female pregnancy
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• response to nicotine
• GO:0010260 Starenje
• positive regulation of fever generation
• Memorija
• negative regulation of action potential
• regulation of feeding behavior
• negative regulation of ion transport
• response to morphine
• negative regulation of fatty acid beta-oxidation
• response to lipopolysaccharide
• positive regulation of blood pressure
• regulation of penile erection
• regulation of lipid metabolic process
• Spermatogeneza
• positive regulation of neuron projection development
• positive regulation of apoptotic process
• positive regulation of acute inflammatory response to antigenic stimulus
• learning or memory
• Nocicepcija
• negative regulation of dopamine secretion
• regulation of synaptic transmission, glutamatergic
• response to ethanol
• axonal fasciculation
• regulation of synaptic transmission, GABAergic
• GO:0072468 Transdukcija signala
• response to cocaine
• trans-synaptic signaling by endocannabinoid, modulating synaptic transmission
• G protein-coupled receptor signaling pathway
• cannabinoid signaling pathway
• retrograde trans-synaptic signaling by endocannabinoid
• positive regulation of presynaptic cytosolic calcium concentration
• induction of synaptic vesicle exocytosis by positive regulation of presynaptic cytosolic calcium ion concentration
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

1268

12801

Ensembl

ENSG00000118432

ENSMUSG00000044288

UniProt

P21554

P47746

RefSeq (mRNK)
NM_001160226
NM_001160258
NM_001160259
NM_001160260
NM_016083

NM_033181
NM_001365869
NM_001365870
NM_001365872
NM_001365874
NM_001370545
NM_001370546
NM_001370547

NM_007726
NM_001355020
NM_001355021
NM_001365881

RefSeq (bjelančevina)
NP_001153698
NP_001153730
NP_001153731
NP_057167
NP_149421

NP_001352798
NP_001352799
NP_001352801
NP_001352803
NP_001357474
NP_001357475
NP_001357476

NP_031752
NP_001341949
NP_001341950
NP_001352810

Lokacija (UCSC)Chr 6: 88.14 – 88.17 MbChr 4: 33.92 – 33.95 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Primarni endogeni agonist ljudskog receptora CB1 je anandamid.[5]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 472 aminokiseline, а molekulska težina 52.858 Da.[8]

1020304050
MKSILDGLADTTFRTITTDLLYVGSNDIQYEDIKGDMASKLGYFPQKFPL
TSFRGSPFQEKMTAGDNPQLVPADQVNITEFYNKSLSSFKENEENIQCGE
NFMDIECFMVLNPSQQLAIAVLSLTLGTFTVLENLLVLCVILHSRSLRCR
PSYHFIGSLAVADLLGSVIFVYSFIDFHVFHRKDSRNVFLFKLGGVTASF
TASVGSLFLTAIDRYISIHRPLAYKRIVTRPKAVVAFCLMWTIAIVIAVL
PLLGWNCEKLQSVCSDIFPHIDETYLMFWIGVTSVLLLFIVYAYMYILWK
AHSHAVRMIQRGTQKSIIIHTSEDGKVQVTRPDQARMDIRLAKTLVLILV
VLIICWGPLLAIMVYDVFGKMNKLIKTVFAFCSMLCLLNSTVNPIIYALR
SKDLRHAFRSMFPSCEGTAQPLDNSMGDSDCLHKHANNAASVHRAAESCI
KSTVKIAKVTMSVSTDTSAEAL

Struktura uredi

Receptor CB1 dijeli strukturu karakterističnu za sve receptore vezane za G-protein, posjedujući sedam transmembranskih domena, povezanih s po tri vanćelijske i unutarćelijske petlje, vanćelijskim N-terminalnim repom i unutarćelijskim C-terminalnim repom.[9][10] Receptor može postojati kao homodimer ili u obliku heterodimera ili drugih GPCR oligomera različitim klasama receptora vezanih za G-protein . Posmatrani heterodimeri uključuju A2A–CB1, CB1–D2, OX1–CB1, dok mnogi drugi mogu biti dovoljno stabilni da postoje i in vivo.[11] Receptor CB1 ima alosternomodulatorsko mjesto vezanja.[12][13]

Mehanizam uredi

Receptor CB1 je predsinapsni heteroreceptor koji modulira oslobađanje neurotransmitera kada se aktivira na dozno ovisan, stereoselektivan i na kašalj osjetljiv na toksine.[14] Receptor CB1 , kao aktivirani kanabinoid, prirodno se generira unutar tijela (endokanabinoidi) ili unosi u tijelo kao kanabis ili srodan sintetski spoj.

Istraživanja pokazuju da je većina receptora CB1 spregnuta preko Gi/o proteina. Nakon aktivacije, ovaj receptor pokazuje svoje učinke uglavnom aktivacijom Gi, koja smanjuje koncentraciju unutarćelijskog cAMP-a, inhibirajući njegovu proizvodnju enzima, adenilat-ciklaza i povećava koncentraciju mitogen-aktivirane protein-kinaze (MAP-kinaze). Alternativno, u nekim rijetkim slučajevima aktivacija receptora CB1 može biti povezana sa Gs proteinima, koji stimuliraju adenilat-ciklaze.[11] Poznato je da cAMP služi kao drugi glasnik, povezan sa različitim ionskim kanalima, uključujući i pozitivno uticajni kalijevi kanali koji se ispravljaju prema unutra (= Kir ili IRK),[15] i kalcijeve kanale , koji se aktiviraju interakcijom ovisnom o cAMP-u molekulama kao što su protein-kinaza A (PKA), protein-kinaza C (PKC), Raf -1, ERK, JNK, p38, c-fos, c-jun i drugi.

U smislu funkcije, inhibicija unutarćelijske ekspresije cAMP skraćuje trajanje predsinapsnih akcijskih potencijala produžavanjem ispravljajućih struja kalijevog A tipa, koje se normalno inaktiviraju pri fosforilacijama pomoću PKA. Ova inhibicija postaje sve izraženija ako se uzme u obzir učinak aktiviranih receptora CB1, kako bi se ograničio unos kalcija u ćeliju, što se ne događa putem cAMP-a, već direktnom inhibicijom posredovanom G-proteinom. Kako je presinapsni unos kalcija uvjet za oslobađanje vezikula, ova funkcija će smanjiti neurotransmiter koji nakon otpuštanja ulazi u sinapsu.[16] Relativna koncentracija ova dva inhibicijska mehanizma ovisi o varijajije ekspresije ionskih kanala po tipovima ćelija.

Relativni doprinos svakog od ova dva inhibitorna mehanizma ovisi o varijansi ekspresije ionskih kanala prema tipu ćelije.

Receptor CB1 također može biti alosterni sinergijski i moduliran sintetskim ligandima[17] na pozitivni[18] i negativni[19] način. In vivo izloženost THC-u narušava dugotrajno potenciranje i dovodi do smanjenja fosforiliranog CREB.[20]

Ukratko, otkriveno je da je aktivnost receptora CB1 povezana s određenim ionskim kanalima, na sljedeći način:[11]

  • Pozitivno na unutrašnju ekspresiju i vanjske kalijeve kanale tipa A.
  • Negativno na vanjske kalijeve kanale D-tipa
  • Negativno na kalcijske kanale N-tipa i P/Q-tipa.

Ekspresija uredi

Receptor CB1 koriran je genom i CNR1,[14] koji se nalazi na hromosomu 6.[16] Opisane su dvije varijante transkripta za kodiranje različitih izoformi.[14] CNR1 ortolozi[21] identificirani su kod većine sisara.

Receptor CB1 eksprimira se presinapsno i na glutaminergičnim i na GABAergičnim interneuronima i, u stvari, djeluje kao neuromodulator za inhibiranje oslobađanja glutamata i GABA. Ponovljena primjena receptorskih agonista može rezultirati internalizacijom receptora i /ili smanjenjem signalizacije proteinskih receptora.

Inverzni agonist MK-9470 omogućava stvaranje in vivo slika distribucije receptora CB1 u ljudskom mozgu pomoću pozitronske emisione tomografije.[22]

Ligandi uredi

Agonisti uredi

Selektivni uredi

Neodređena efikasnost uredi

Parcijalni uredi

Endogeni uredi
Fito/sintetski uredi

Potpuni uredi

Alosterni agonist uredi

Antagonisti uredi

Inverzni agonisti uredi

Alosterni modulatori uredi

Afinitet vezanja uredi

Afinitet CB1 (Ki) Efikasnost prema CB1 Efikasnost CB2 (Ki) Efikasnost prema CB2 Tip Reference
Anandamid 78 nM Parcijalni agonist 370 nM Parcijalni agonist Endogeni
N-Arahidonoil-dopamin 250 nM Agonist 12000 nM ? Endogeni [26]
2-Arahidonoilglicerol 58,3 nM Potpuni agonist 145 nM Potpuni agonist Endogeni [26]
2-Arahidonil-gliceril eter 21 nM Potpuni agonist 480 nM Potpuni agonist Endogeni
Tetrahidrokanabinol 10 nM Parcijalni agonist 24 nM Parcijalni agonist Fitogeni [27]
EGCG 33600 nM Agonist 50000+ nM ? Fitogeni
AM-1221 52,3 nM Agonist 0,28 nM Agonist Sintetski [28]
AM-1235 1,5 nM Agonist 20,4 nM Agonist Sintetski [29]
AM-2232 0,28 nM Agonist 1,48 nM Agonist Sintetski [29]
UR-144 150 nM Potpuni agonist 1,8 nM Potpuni agonist Sintetski [30]
JWH-007 9,0 nM Agonist 2,94 nM Agonist Sintetski [31]
JWH-015 383 nM Agonist 13,8 nM Agonist Sintetski [31]
JWH-018 9,00 ± 5.00 nM Potpuni agonist 2,94 ± 2,65 nM Potpuni agonist Sintetski [32]

Evolucija uredi

Gen CNR1 koristi se kod životinja kao filogenetski marker jedarnne DNK.[21] Ovaj gen bez introna prvi je put korišten za istraživanje filogeneze glavnih grupa sisara,[33] i doprinijeli otkrivanju da su placentni redovi raspoređeni u pet glavnih klasa: Xenarthra, Afrotheria, Laurasiatheria, Euarchonta i Glires. CNR1 se također pokazao korisnim na nižim taksonomskim nivoima, kao što su glodari,[34][35] i za identifikaciju dermoptera, kao najbližih srodnika primata.[36]

Takođerpogledajte uredi

Reference uredi

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118432 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000044288 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Abood M, Barth F, Bonner TI, Cabral G, Casellas P, Cravatt BF, Devane WA, Elphick MR, Felder CC, Herkenham M, Howlett AC, Kunos G, Mackie K, Mechoulam R, Pertwee RG (22. 8. 2018). "CB1 Receptor". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Pristupljeno 9. 11. 2018.
  6. ^ Thomas A, Stevenson LA, Wease KN, Price MR, Baillie G, Ross RA, Pertwee RG (decembar 2005). "Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist". British Journal of Pharmacology. 146 (7): 917–26. doi:10.1038/sj.bjp.0706414. PMC 1751228. PMID 16205722.
  7. ^ Pertwee RG, Thomas A, Stevenson LA, Ross RA, Varvel SA, Lichtman AH, et al. (mart 2007). "The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo". British Journal of Pharmacology. 150 (5): 586–94. doi:10.1038/sj.bjp.0707124. PMC 2189766. PMID 17245367.
  8. ^ "UniProt, P21554" (jezik: engleski). Pristupljeno 7. 10. 2021.
  9. ^ Shao Z, Yin J, Chapman K, Grzemska M, Clark L, Wang J, Rosenbaum DM (2016). "High-resolution crystal structure of the human CB1 cannabinoid receptor". Nature. 540 (7634): 602–606. Bibcode:2016Natur.540..602S. doi:10.1038/nature20613. PMC 5433929. PMID 27851727.
  10. ^ Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ (2016). "Crystal Structure of the Human Cannabinoid Receptor CB1". Cell. 167 (3): 750–762.e14. doi:10.1016/j.cell.2016.10.004. PMC 5322940. PMID 27768894.
  11. ^ a b c Pertwee RG (april 2006). "The pharmacology of cannabinoid receptors and their ligands: an overview". International Journal of Obesity. 30 Suppl 1: S13–8. doi:10.1038/sj.ijo.0803272. PMID 16570099.
  12. ^ Nickols HH, Conn PJ (januar 2014). "Development of allosteric modulators of GPCRs for treatment of CNS disorders". Neurobiology of Disease. 61: 55–71. doi:10.1016/j.nbd.2013.09.013. PMC 3875303. PMID 24076101.
  13. ^ Nguyen T, Li JX, Thomas BF, Wiley JL, Kenakin TP, Zhang Y (novembar 2016). "Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor". Medicinal Research Reviews. 37 (3): 441–474. doi:10.1002/med.21418. PMC 5397374. PMID 27879006.
  14. ^ a b c "Entrez Gene: CNR1 cannabinoid receptor 1 (brain)".
  15. ^ Demuth DG, Molleman A (januar 2006). "Cannabinoid signalling". Life Sciences. 78 (6): 549–63. doi:10.1016/j.lfs.2005.05.055. PMID 16109430.
  16. ^ a b Elphick MR, Egertová M (mart 2001). "The neurobiology and evolution of cannabinoid signalling". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 356 (1407): 381–408. doi:10.1098/rstb.2000.0787. PMC 1088434. PMID 11316486.
  17. ^ Price MR, Baillie GL, Thomas A, Stevenson LA, Easson M, Goodwin R, McLean A, McIntosh L, Goodwin G, Walker G, Westwood P, Marrs J, Thomson F, Cowley P, Christopoulos A, Pertwee RG, Ross RA (novembar 2005). "Allosteric modulation of the cannabinoid CB1 receptor". Molecular Pharmacology. 68 (5): 1484–95. doi:10.1124/mol.105.016162. PMID 16113085. S2CID 17648541.
  18. ^ Navarro HA, Howard JL, Pollard GT, Carroll FI (april 2009). "Positive allosteric modulation of the human cannabinoid (CB) receptor by RTI-371, a selective inhibitor of the dopamine transporter". British Journal of Pharmacology. 156 (7): 1178–84. doi:10.1111/j.1476-5381.2009.00124.x. PMC 2697692. PMID 19226282.
  19. ^ Horswill JG, Bali U, Shaaban S, Keily JF, Jeevaratnam P, Babbs AJ, Reynet C, Wong Kai In P (novembar 2007). "PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats". British Journal of Pharmacology. 152 (5): 805–14. doi:10.1038/sj.bjp.0707347. PMC 2190018. PMID 17592509.
  20. ^ Fan N, Yang H, Zhang J, Chen C (februar 2010). "Reduced expression of glutamate receptors and phosphorylation of CREB are responsible for in vivo Δ9-THC exposure-impaired hippocampal synaptic plasticity". Journal of Neurochemistry. 112 (3): 691–702. doi:10.1111/j.1471-4159.2009.06489.x. PMC 2809144. PMID 19912468.
  21. ^ a b "OrthoMaM phylogenetic marker: CNR1 coding sequence". Arhivirano s originala, 22. 12. 2015. Pristupljeno 23. 11. 2009.
  22. ^ Burns HD, Van Laere K, Sanabria-Bohórquez S, Hamill TG, Bormans G, Eng WS, Gibson R, Ryan C, Connolly B, Patel S, Krause S, Vanko A, Van Hecken A, Dupont P, De Lepeleire I, Rothenberg P, Stoch SA, Cote J, Hagmann WK, Jewell JP, Lin LS, Liu P, Goulet MT, Gottesdiener K, Wagner JA, de Hoon J, Mortelmans L, Fong TM, Hargreaves RJ (juni 2007). "[18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor". Proceedings of the National Academy of Sciences of the United States of America. 104 (23): 9800–5. Bibcode:2007PNAS..104.9800B. doi:10.1073/pnas.0703472104. PMC 1877985. PMID 17535893.
  23. ^ Lopez-Rodriguez AB, Siopi E, Finn DP, Marchand-Leroux C, Garcia-Segura LM, Jafarian-Tehrani M, Viveros MP (januar 2015). "CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced neuroprotection following traumatic brain injury in mice". Cerebral Cortex. 25 (1): 35–45. doi:10.1093/cercor/bht202. PMID 23960212.
  24. ^ Leggett JD, Aspley S, Beckett SR, D'Antona AM, Kendall DA, Kendall DA (2004). "Oleamide is a selective endogenous agonist of rat and human CB1 cannabinoid receptors". Br J Pharmacol. 141 (2): 253–62. doi:10.1038/sj.bjp.0705607. PMC 1574194. PMID 14707029.
  25. ^ Laprairie RB, Kulkarni PM, Deschamps JR, Kelly ME, Janero DR, Cascio MG, Stevenson LA, Pertwee RG, Kenakin TP, Denovan-Wright EM, Thakur GA (februar 2017). "Enantiospecific Allosteric Modulation of Cannabinoid 1 Receptor". ACS Chemical Neuroscience. 8 (6): 1188–1203. doi:10.1021/acschemneuro.6b00310. PMID 28103441.
  26. ^ a b Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA (decembar 2010). "International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂". Pharmacological Reviews. 62 (4): 588–631. doi:10.1124/pr.110.003004. PMC 2993256. PMID 21079038.
  27. ^ "PDSP Database – UNC". Arhivirano s originala, 8. 11. 2013. Pristupljeno 11. 6. 2013.
  28. ^ Šablon:Ref patent2
  29. ^ a b Šablon:Ref patent2
  30. ^ 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 (januar 2010). "Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity". Journal of Medicinal Chemistry. 53 (1): 295–315. doi:10.1021/jm901214q. PMID 19921781.
  31. ^ 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 CB(1) and CB(2) receptor binding". Drug and Alcohol Dependence. 60 (2): 133–40. doi:10.1016/S0376-8716(99)00152-0. PMID 10940540.
  32. ^ 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 and Alcohol Dependence. 60 (2): 133–40. doi:10.1016/s0376-8716(99)00152-0. PMID 10940540.
  33. ^ Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O'Brien SJ (februar 2001). "Molecular phylogenetics and the origins of placental mammals". Nature. 409 (6820): 614–8. Bibcode:2001Natur.409..614M. doi:10.1038/35054550. PMID 11214319. S2CID 4373847.
  34. ^ Blanga-Kanfi S, Miranda H, Penn O, Pupko T, DeBry RW, Huchon D (april 2009). "Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades". BMC Evolutionary Biology. 9: 71. doi:10.1186/1471-2148-9-71. PMC 2674048. PMID 19341461.
  35. ^ DeBry RW (oktobar 2003). "Identifying conflicting signal in a multigene analysis reveals a highly resolved tree: the phylogeny of Rodentia (Mammalia)". Systematic Biology. 52 (5): 604–17. doi:10.1080/10635150390235403. PMID 14530129.
  36. ^ Janecka JE, Miller W, Pringle TH, Wiens F, Zitzmann A, Helgen KM, Springer MS, Murphy WJ (novembar 2007). "Molecular and genomic data identify the closest living relative of primates". Science. 318 (5851): 792–4. Bibcode:2007Sci...318..792J. doi:10.1126/science.1147555. PMID 17975064. S2CID 12251814.

Vanjski linkovi uredi

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=CNR1&oldid=3371144"