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Kanabinoidni receptor tip 1 — разлика између измена

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Ред 3:
 
== Struktura ==
CB<sub>1</sub> receptor ima zajedničke strukturne karakteristike svih G protein spregnutih receptora. On poseduje [[Sedam-transmembranski domen receptori|sedam transmembranskih domena]] povezanih sa tri ekstracelularne i tri intracelularne petlje, ekstracelularni [[N-terminus|-{N}--terminus]], i intracelularni [[C-terminus|-{C}--terminus]].<ref name="pmid11316486">{{Cite journal|last= Elphick |first= M. R.|last2 = Egertova |first2 = M.
|last1 = Elphick |first1 = M. R.
|last2 = Egertova |first2 = M.
| title = The neurobiology and evolution of cannabinoid signalling
| doi = 10.1098/rstb.2000.0787
| journal = Philosophical Transactions of the Royal Society B: Biological Sciences
| volume = 356
| issue = 1407|pages= 381–408|year = 2001
| pages = 381–408
| year = 2001
| pmc = 1088434
| pmid = 11316486
}}</ref> Ovi receptori mogu da postoje kao [[Proteinski dimer|homodimeri]], [[Proteinski dimer|heterodimeri]] ili [[oligomer]]i kad su koizraženi sa jednom ili više klasa G protein spregnutih receptora. Uočeni heterodimeri su -{A<sub>2A</sub>CB<sub>1</sub>, A<sub>2A</sub>, CB<sub>1</sub>D<sub>2</sub>}-, oreksin -{1/CB1, CB1/D2,}-. Mnogi drugi su možda stabilni jedino in vivo.<ref name="pmid16570099">{{Cite journal|last= Pertwee |first= R. G.
|last1 = Pertwee |first1 = R. G.
| doi = 10.1038/sj.ijo.0803272
| title = The pharmacology of cannabinoid receptors and their ligands: An overview
| journal = International Journal of Obesity
| volume = 30|pages= S13–S18|year = 2006
| pages = S13–S18
| year = 2006
| pmid = 16570099
}}</ref> Postoje dokaza da ovi receptori poseduju [[Alosterna regulacija|alosterno]] mesto vezivanja, koje može da postane biološki cilj za poboljšanje kliničkih modulatornih efekata kanabinoida.<ref name="pmid16570099"/>
Линија 29 ⟶ 22:
CB<sub>1</sub> receptor je presinaptički [[heteroreceptor]] koji moduliše otpuštanje neurotransmitera kad je aktiviran. On funkcioniše na način koji je zavistan od doze, stereoselektivan i senzitivan na [[pertuzijski toksin]].<ref name="entrez" /> CB<sub>1</sub> receptor aktiviraju [[kanabinoid]]i, prirodno formirani u telu ([[Endokanabinoidi]]) ili uneseni kao [[kanabis (lek)|kanabis]] ili srodno [[Hemijska sinteza|sintetičko]] jedinjenje.
 
Iz istraživanja proizilazi da je većina CB<sub>1</sub> receptora spregnuta sa -{G<sub>i/o</sub>}- proteinima. Pri aktivaciji, CB<sub>1</sub> receptor deluje prvenstveno putem aktivacije [[Gi alfa podjedinica|-{G<sub>i</sub>}-]], čime se snižava intracelularna cAMP koncentracija putem inhibicije [[enzim]]a za njegovu produkciju, [[adenilat ciklaza|adenilat ciklaze]], i povišava koncentracija [[mitogenom-aktivirane proteinske kinaze]] (MAP kinaze). Alternativno, u nekim retkim slučajevima aktivacija CB<sub>1</sub> receptora može da bude spregnuta sa [[Gs alfa podjedinica|-{G<sub>s</sub>}-]] proteinima, koji stimulišu [[adenilat ciklaza|adenilat ciklazu]].<ref name="pmid16570099"/> Poznato je da cAMP služi kao sekundarni glasnik koji se spreže sa mnoštvom jonskih kanala, uključujući [[unutrašnje ispravljajući kalijumski kanali|unutrašnje ispravljajuće kalijumske kanale]] (Kir ili IRK),<ref name="pmid16109430">{{Cite journal|last= Demuth |first= D.|last2 = Molleman |first2 = A.
|last1 = Demuth |first1 = D.
|last2 = Molleman |first2 = A.
| title = Cannabinoid signalling
| journal = Life Sciences
| volume = 78
| issue = 6
| pages = 549–563
| year = 2006
| pmid = 16109430
| doi = 10.1016/j.lfs.2005.05.055
}}</ref> i [[kalcijumov kanal|kalcijumove kanale]], koji se aktiviraju cAMP zavisnom interakcijom sa molekulima poput [[proteinska kinaza A|proteinske kinaze A]] (PKA), [[proteinska kinaza C|proteinske kinaze C]] (PKC), [[C-Raf|Raf-1]], [[Ekstracelularnim signalom regulisana kinaza|ERK]], [[c-Jun N-terminalne kinaze|JNK]], [[p38 mitogenom aktivirana proteinske kinaze|p38]], [[c-fos]], [[c-jun]] i drugim.<ref name="endocrino">{{Cite journal|last2 = Marsicano|first= U.
|last2 author2= Marsicano |first1first2 = UG.
| author3=Cota|last4 = Lutz|last3 = Cota|last5 = Pasquali |first3 = D.▼
| author2 = Marsicano |first2 = G.
|last1 author4=Lutz|last= Pagotto |first4 = B.▼
| author3 = Cota
| author5 = Pasquali |first5 = R.▼
|last4 = Lutz
|last3 = Cota
▲|last5 = Pasquali |first3 = D.
| author4 = Lutz
▲|last1 = Pagotto |first4 = B.
▲| author5 = Pasquali |first5 = R.
| title = The emerging role of the endocannabinoid system in endocrine regulation and energy balance
| journal = Endocrine Reviews
| volume = 27
| issue = 1
| pages = 73–100
| year = 2006
| pmid = 16306385
Линија 60 ⟶ 46:
}}</ref> Funkcionalno, inhibicija intraćelijskog cAMP izražavanja skraćuje trajanje presinaptičkog akcionog potencijala, produžavajući kalijumske struje A-tipa, što je normalno inaktivirano nakon fosforilacije PKA-om. Ova inhibicija postaje izraženija pri aktivaciji CB<sub>1</sub> receptora da bi se ograničio ulaz kalcijuma u ćeliju. Pošto je presinaptički ulaz kalcijuma neophodan za otpuštanje vezikule, ova funkcija će umanjiti ulaz trasmitera u sinapse.<ref name="pmid11316486"/> Relativni doprinos svakog od ova dva inhibitorna mehanizam zavisi od varijanse izražavanja jonskih kanala u datom ćelijskom tipu.
 
CB<sub>1</sub> receptor se može modulisati putem [[Alosterna regulacija|alosternih]] sintetičkih liganda<ref name="pmid16113085">{{cite journal |vauthors=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 | title = Allosteric modulation of the cannabinoid CB1 receptor | journal = Mol. Pharmacol. | volume = 68 | issue = 5 | pages = 1484–95 | year = 2005 | pmid = 16113085 | doi = 10.1124/mol.105.016162 | url = }}</ref> u pozitivnom<ref name="pmid19226282">{{cite journal |vauthors=Navarro HA, Howard JL, Pollard GT, Carroll FI | title = Positive allosteric modulation of the human cannabinoid (CB1) receptor by RTI-371, a selective inhibitor of the dopamine transporter | journal = Br. J. Pharmacol. | volume = 156 | issue = 7 | pages = 1178–84 | year = 2009 | pmid = 19226282 | pmc = 2697692 | doi = 10.1111/j.1476-5381.2009.00124.x | url = }}</ref> i negativnom<ref name="pmid17592509">{{cite journal |vauthors=Horswill JG, Bali U, Shaaban S, Keily JF, Jeevaratnam P, Babbs AJ, Reynet C, Wong Kai In P | title = PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats | journal = Br. J. Pharmacol. | volume = 152 | issue = 5 | pages = 805–14 | year = 2007 | pmid = 17592509 | pmc = 2190018 | doi = 10.1038/sj.bjp.0707347 | url = }}</ref> maniru. ''[[In vivo]]'' izlaganje [[Tetrahidrokanabinol|THC]] ligandu umanjuje [[dugotrajna potencijacija|dugotrajnu potencijaciju]] i dovodi do redukcije fosforilisanog [[CREB]].<ref name="neurochem">{{cite journal |vauthors=Fan N, Yang H, Zhang J, Chen C | title = Reduced expression of glutamate receptors and phosphorylation of CREB are responsible for in vivo Δ9-THC exposure-impaired hippocampal synaptic plasticity | journal = J. Neurochem. | volume = 112 | issue = 3 | pages = 691–702 | year = 2010 | pmid = 19912468 | pmc = 2809144 | doi = 10.1111/j.1471-4159.2009.06489.x | url = }}</ref>
 
Ukratko, aktivnost CB<sub>1</sub> receptora je spregnuta sa jonskim kanalima, na sledeći način:<ref name="pmid16570099"/>
Линија 72 ⟶ 58:
-{CB}-<sub>1</sub> receptor je izražen presinaptički na glutaminergičnim i GABAergičnim neuronima i efektivno deluje kao [[neuromodulator]] koji inhibira otpuštanje [[glutamat]]a i [[GABA]].<ref name="pmid11316486"/> Višestruka administracija agonista može da dovede do internalizacije i/ili redukcije signalizacije receptora.<ref name="pmid16570099"/>
 
[[Inverzni agonist]] -{[[MK-9470]]}- omogućava formiranje ''in vivo'' slika distribucije CB<sub>1</sub> receptora u ljudskom mozgu pomoću [[Pozitronska emisiona tomografija|pozitronske emisione tomografije]].<ref name="pmid17535893">{{Cite journal|last2 = Van Laere|first= H. .|last2=Laere|first2=Van|first2 = K. .
| author3=Sanabria-bohórquez|last4 = Hamill|last3 = Sanabria-Bohórquez|last5 = Bormans |first3 = S. .
|last2 = Van Laere|first1 = H. .
| author2 author4= Van LaereHamill |first2first4 = KT. .|last7 = Gibson
| author5=Bormans|last8 = Ryan |first5 = G. .|last= Burns|last9 = Connolly |first6 = W. .
| author3 = Sanabria-bohórquez
| author7=Gibson|last6 = Eng▼
|last4 = Hamill
| author6 = Eng |first7 = R. .▼
|last3 = Sanabria-Bohórquez
|last5 author8= BormansRyan |first3first8 = SC. .
| author4 author9= HamillConnolly |first4first9 = TB. .
|last7 = Gibson
| author5 = Bormans
|last8 = Ryan |first5 = G. .
|last1 = Burns
|last9 = Connolly |first6 = W. .
| author7 = Gibson
▲|last6 = Eng
▲| author6 = Eng |first7 = R. .
| author8 = Ryan |first8 = C. .
| author9 = Connolly |first9 = B. .
| title = 18FMK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor
| journal = Proceedings of the National Academy of Sciences of the United States of America
| volume = 104
| issue = 23
| pages = 9800–9805
| year = 2007
| pmc = 1877985
Линија 109 ⟶ 85:
{{PBB_Further_reading
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}}
{{refend}}
 
== Spoljašnje veze ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2205 | title = Cannabinoid Receptors: CB<sub>1</sub> | accessdate = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
{{-}}
{{G protein spregnuti receptori-lat}}
Преузето из „https://sr.wikipedia.org/wiki/Kanabinoidni_receptor_tip_1”