Adenozinski A2A receptor

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Adenozinski A2A receptor
Kristalografska struktura adenozinskog A2A receptora (N-terminus = plavo, C-terminus = crveno) u kompleksu sa ZM-241,385 (štapićasti dijagram), bazirana na 3EML​ koordinatama.
Dostupne strukture
3EML​
Identifikatori
Simboli ADORA2A; ADORA2; RDC8; hA2AR
Vanjski ID OMIM: 102776 MGI: 99402 HomoloGene: 20166 IUPHAR: A2A GeneCards: ADORA2A Gene
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 135 11540
Ensembl ENSG00000128271 ENSMUSG00000020178
UniProt P29274 Q2NLC1
RefSeq (mRNA) NM_000675 NM_009630
RefSeq (protein) NP_000666 NP_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) je adenozinski receptor. On je kodiran humanim ADORA2A genom.[1][2]

Struktura[uredi | uredi izvor]

Ovaj protein je član familije G protein-spregnutih receptora koji imaju sedam transmembranskih alfa heliksa. Kristalografska struktura adenozinskog A2A receptora (3EML​) pokazuje da je mesto vezivanja liganda distinktno u odnosu na druge GPCR proteine sa određenom strukturom (npr., beta-2 adrenergički receptor i rodopsin).[3]

Heteromeri[uredi | uredi izvor]

Dejstva A2A receptora su komplikovana činjenicom da je mnoštvo funkcionalnih heteromera, 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] dopaminski D2/A2A[6] iD3/A2A,[7] glutamatni mGluR5/A2A[8] i kanabinoidni CB1/A2A[9] su zapaženi, kao i CB1/A2A/D2 heterotrimeri.[10] Istraživanje funkcionalnog značaja i endogene uloge tih hibridnih receptora je u toku.[11][12][13]

Funkcija[uredi | uredi izvor]

Ovaj protein je jedan od nekoliko podtipova adenozinskih receptora. Njegova aktivnost je posredovana G proteinima koji aktiviraju adenilat ciklazu. Ovog proteina ima u izobilju u bazalnoj gangliji, vaskulaturi i krvnim pločicama. On je jedan od glavnih meta kofeina.[14]

Fiziološka uloga[uredi | uredi izvor]

Poput A1, A2A receptori učestvuju u regulaciji potrošnje miokardijalnog kiseonika i koronarnog krvnog protoka.

A2A receptor je odgovoran za regulaciju miokardijalnog protoka krvi putem vazodilatacije koronarnih arterija, čime se povećava krvni protok do miokardijuma, 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 lečenje insomnije, bola, depresije, zavisnosti od droge i Parkinsonove bolesti.[15][16][17][18][19][20][21]

Ligandi[uredi | uredi izvor]

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 neselektivni antagonisti adenozinskog receptora kao što je aminofilin, su bili usredsređeni na ulogu adenozinskih receptora u funkciji srca. To je rezultovalo u nekoliko kliničkih ispitivanja tih antagonista za lečenje bradikardijskog srčanog 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 lečenju Parkinsonove bolesti.[47][48][49][50]

Agonisti[uredi | uredi izvor]

Antagonisti[uredi | uredi izvor]

Interakcije[uredi | uredi izvor]

Za adenozinski A2A receptor je pokazano da interaguje sa dopaminskim receptorom D2.[58]

Reference[uredi | uredi izvor]

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