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Adenozinski A2A receptor

С Википедије, слободне енциклопедије
Adenozinski A2A receptor
Kristalografska struktura adenozinskog A2A receptora (N-terminus = plavo,C-terminus = crveno) u kompleksu saZM-241,385 (štapićasti dijagram), bazirana na3EML​ koordinatama.
Dostupne strukture
3EML​
Identifikatori
SimboliADORA2A; ADORA2; RDC8; hA2AR
Vanjski IDOMIM: 102776MGI: 99402HomoloGene: 20166IUPHAR:A2AGeneCards:ADORA2A Gene
Ontologija gena
Molekularna funkcija•aktivnost rodopsinu-sličnog receptora
•aktivnost A2A adenozinskog receptora, G-protein spregnutog
•receptorska aktivnost
•aktivnost gastričnog inhibitornog peptidnog receptora
Celularna komponenta•membranska frakcija
•ćelijska membrana
•integralno sa ćelijskom membranom
•membrana
•integralno sa membranom
Biološki proces•sinaptička transmisija, dopaminergička
•signalni put adenozinskog receptora
•cAMP biosintetički proces
•transport neurotransmitera
•fagocitoza
•apoptoza
•inflamatorni respons
•celularni odbrambeni respons
•prenos signala
•signalni put G-protein spregnutog receptora
•aktivacija adenilat ciklaze
•interćelijska signalizacija
•razvoj centralnog nervnog sistema
•koagulacija krvi
•senzorna percepcija
•lokomotorno ponašanje
•cirkulacija
•način ishrane
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez13511540
EnsemblENSG00000128271ENSMUSG00000020178
UniProtP29274Q2NLC1
RefSeq (mRNA)NM_000675NM_009630
RefSeq (protein)NP_000666NP_033760
Lokacija (UCSC)Chr 22:
23.15 - 23.17 Mb		Chr 10:
74.77 - 74.78 Mb
PubMed pretraga[1][2]

Adenozinski A2A receptor (ADORA2A) jeadenozinski receptor. On je kodiran humanimADORA2Agenom.[1][2]

Struktura

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Ovaj protein je član familijeG protein-spregnutih receptora koji imaju sedam transmembranskihalfa heliksa.Kristalografska struktura adenozinskog A2A receptora (3EML​) pokazuje da je mesto vezivanjaliganda distinktno u odnosu na druge GPCR proteine sa određenom strukturom (npr.,beta-2 adrenergički receptor irodopsin).[3]

Heteromeri

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Dejstva A2A receptora su komplikovana činjenicom da je mnoštvo funkcionalnihheteromera, koji su kombinacije A2A podjedinica i drugih nesrodnih G-protein spregnutih receptora, nađeno u mozgu. To uvećava kompleksnost uloge adenozina u modulaciji neuronske aktivnosti. Heteromeri koji sadrže adenozinski A1/A2A,[4][5] dopaminskiD2/A2A[6] iD3/A2A,[7] glutamatnimGluR5/A2A[8] i kanabinoidniCB1/A2A[9] su zapaženi, kao i CB1/A2A/D2heterotrimeri.[10] Istraživanje funkcionalnog značaja iendogene uloge tih hibridnih receptora je u toku.[11][12][13]

Funkcija

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Ovaj protein je jedan od nekoliko podtipovaadenozinskih receptora. Njegova aktivnost je posredovanaG proteinima koji aktivirajuadenilat ciklazu. Ovog proteina ima u izobilju u bazalnoj gangliji,vaskulaturi ikrvnim pločicama. On je jedan od glavnih metakofeina.[14]

Fiziološka uloga

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PoputA1, A2A receptori učestvuju u regulaciji potrošnje miokardijalnog kiseonika i koronarnog krvnog protoka.

A2A receptor je odgovoran za regulaciju miokardijalnog protoka krvi putemvazodilatacijekoronarnih arterija, čime se povećava krvni protok domiokardijuma, mada to može da dovede do hipotenzije. Kao i A1 receptori, ovo dejstvo normalno služi kao zaštitni mehanizam.

A2A receptori su izraženi u mozgu, gde regulišu glutamatno i dopaminsko oslogađanje. On je potencijalna terapeutska meta za lečenjeinsomnije, bola,depresije,zavisnosti od droge iParkinsonove bolesti.[15][16][17][18][19][20][21]

Ligandi

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Brojni selektivni A2A ligandi su razvijeni,[22][23][24][25][26][27][28][29][30][31][32][33] sa nekoliko mogućih terapeutskih primena.[34][35][36][37][38][39] Starija ispitivanja funkcije adenozinskog receptora, i neselektivniantagonisti adenozinskog receptora kao što jeaminofilin, su bili usredsređeni na ulogu adenozinskih receptora u funkciji srca. To je rezultovalo u nekoliko kliničkih ispitivanja tih antagonista za lečenjebradikardijskogsrčanog zastoja.[40][41][42][43][44][45][46]

Međutim razvoj selektivnijih A2A liganda je doveo do drugih primena. Najznačajniji fokus istraživanja je potencijalna terapeutska uloga A2A antagonista u lečenjuParkinsonove bolesti.[47][48][49][50]

Agonisti

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Antagonisti

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Interakcije

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Za adenozinski A2A receptor je pokazano dainteraguje sadopaminskim receptorom D2.[58]

Reference

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Literatura

[уреди |уреди извор]
Klasa A:Rodopsinu slični
Neurotransmiter
Adrenergički
α1 (A,B,D) • α2 (A,B,C) • β1 • β2 • β3
Purinski
Serotoninski
(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
Eikozanoidni
CysLT (1,2) • LTB4 (1,2) • FPRL1 • OXE • Prostaglandin (DP (1,2),EP (1,2,3,4),FP) • Prostaciklin • Tromboksan
Drugi
Peptid
Neuropeptidni
B/W (1,2) • FF (1,2) • S • Y (1,2,4,5) • Neuromedin (B,U (1,2)) • Neurotenzin (1,2)
Drugi
Razno
Orfan
Drugi
Klasa B:Sekretinu slični
Orfan
Drugi
Klasa C:Metabotropni
glutamat /feromon
Ukus
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
Zaglađeni
Adenozinski A2A receptor nasrodnim projektima Vikipedije:
Mediji na Ostavi
Podaci na Vikipodacima
Преузето из „https://sr.wikipedia.org/w/index.php?title=Adenozinski_A2A_receptor&oldid=30638385”
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