Nomenclature: A2A receptor

Family: Adenosine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 412 22q11.23 ADORA2A adenosine A2a receptor 34,61,93
Mouse 7 410 10 Adora2a adenosine A2a receptor 73
Rat 7 410 20p12 Adora2a adenosine A2a receptor 15
Previous and Unofficial Names
A2a
ADORA2
RDC8
A2ar
Adenosine A2a-receptor
adenosine receptor A2a
A2AAR
AA2AR
Rs
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Human A2A adenosine receptor bound to an antagonist
PDB Id:  4EIY
Ligand:  ZM-241385
Resolution:  1.8Å
Species:  Human
References:  68
Image of receptor 3D structure from RCSB PDB
Description:  A2A receptor (thermostabilised) bound to its natural ligand adenosine
PDB Id:  2YDO
Ligand:  adenosine   This ligand is endogenous
Resolution:  3.0Å
Species:  Human
References:  63
Image of receptor 3D structure from RCSB PDB
Description:  Thermostabilised human A2A receptor with NECA bound
PDB Id:  2YDV
Ligand:  NECA
Resolution:  2.6Å
Species:  Human
References:  62
Natural/Endogenous Ligands
adenosine
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]CGS 21680 Hs Full agonist 7.7 – 7.8 pKd 45,125
pKd 7.7 – 7.8 (Kd 1.6x10-8 – 2.2x10-8 M) [45,125]
[3H]NECA Hs Full agonist 7.7 pKd 55
pKd 7.7 [55]
apadenoson Hs Agonist 9.3 pKi 92
pKi 9.3 (Ki 5x10-10 M) [92]
(R,S)-PHPNECA Hs Full agonist 8.5 pKi 124
pKi 8.5 [124]
2-hexynyl-NECA Hs Full agonist 8.2 – 8.3 pKi 23,57,124
pKi 8.2 – 8.3 [23,57,124]
NECA Rn Agonist 8.01 pKi 70
pKi 8.01 (Ki 9.7x10-9 M) [70]
NECA Hs Full agonist 6.9 – 8.7 pKi 8,23,38,52,57,128
pKi 6.9 – 8.7 [8,23,38,52,57,128]
CGS 21680 Rn Agonist 7.72 pKi 67
pKi 7.72 (Ki 1.9x10-8 M) [67]
CGS 21680 Hs Full agonist 6.7 – 8.1 pKi 8,23,38,44,52,55,57,86
pKi 6.7 – 8.1 [8,23,38,44,52,55,57,86]
2-chloroadenosine Rn Agonist 7.12 pKi 20
pKi 7.12 (Ki 7.6x10-8 M) [20]
CV-1808 Hs Full agonist 7.1 pKi 23,57
pKi 7.1 [23,57]
adenosine Rn Agonist 6.82 pKi 128
pKi 6.82 (Ki 1.5x10-7 M) [128]
2-chloroadenosine Hs Full agonist 6.7 – 6.8 pKi 52,57
pKi 6.7 – 6.8 [52,57]
TCPA Hs Agonist 6.68 pKi 5
pKi 6.68 (Ki 2.1x10-7 M) [5]
(R)-PIA Rn Agonist 6.66 pKi 20
pKi 6.66 (Ki 2.2x10-7 M) [20]
binodenoson Hs Agonist 6.57 pKi 44
pKi 6.57 (Ki 2.7x10-7 M) [44]
regadenoson Hs Agonist 6.54 pKi 44
pKi 6.54 (Ki 2.9x10-7 M) [44]
adenosine Hs Agonist 6.51 pKi 30-31,128
pKi 6.51 (Ki 3.1x10-7 M) [30-31,128]
CGS 24012 Hs Full agonist 6.4 pKi 52
pKi 6.4 [52]
N(6)-cyclohexyladenosine Rn Agonist 6.34 pKi 20
pKi 6.34 (Ki 4.6x10-7 M) [20]
Cl-IB-MECA Rn Agonist 6.33 pKi 67
pKi 6.33 (Ki 4.7x10-7 M) [67]
PENECA Hs Full agonist 6.2 pKi 124
pKi 6.2 [124]
cyclopentyladenosine Hs Full agonist 6.1 pKi 38,44,55
pKi 6.1 [38,44,55]
(R)-PIA Hs Full agonist 6.0 – 6.2 pKi 23,38,52,55,57
pKi 6.0 – 6.2 [23,38,52,55,57]
cyclopentyladenosine Rn Agonist 6.02 pKi 67
pKi 6.02 (Ki 9.5x10-7 M) [67]
CCPA Rn Agonist 6.02 pKi 67
pKi 6.02 (Ki 9.5x10-7 M) [67]
MRS3558 Rn Agonist 5.97 pKi 67
pKi 5.97 (Ki 1.08x10-6 M) [67]
IB-MECA Hs Full agonist 5.6 – 6.3 pKi 44,52,55
pKi 5.6 – 6.3 [44,52,55]
HEMADO Hs Agonist 5.92 pKi 56,124
pKi 5.92 (Ki 1.2x10-6 M) [56,124]
N(6)-cyclohexyladenosine Hs Full agonist 5.9 pKi 23,57
pKi 5.9 [23,57]
GR79236 Hs Agonist 5.89 pKi 44
pKi 5.89 (Ki 1.3x10-6 M) [44]
CV-1674 Hs Full agonist 5.8 pKi 57
pKi 5.8 [57]
tecadenoson Hs Agonist 5.64 pKi 44
pKi 5.64 (Ki 2.315x10-6 M) [44]
MRS3558 Hs Agonist 5.63 pKi 44
pKi 5.63 (Ki 2.33x10-6 M) [44]
CCPA Hs Full agonist 5.6 pKi 44,55
pKi 5.6 [44,55]
metrifudil Hs Full agonist 5.5 pKi 57
pKi 5.5 [57]
AB-MECA Hs Full agonist 5.4 pKi 55
pKi 5.4 [55]
APNEA Hs Full agonist 5.3 pKi 57
pKi 5.3 [57]
Cl-IB-MECA Hs Agonist 5.27 pKi 44
pKi 5.27 (Ki 5.36x10-6 M) [44]
(S)-PIA Hs Full agonist 5.0 – 5.1 pKi 23,55
pKi 5.0 – 5.1 [23,55]
MRS5151 Hs Agonist <5.0 pKi 75
pKi <5.0 (Ki >1x10-5 M) [75]
MRS5151 Mm Agonist <5.0 pKi 75
pKi <5.0 (Ki >1x10-5 M) [75]
Cl-IB-MECA Mm Agonist ~5.0 pKi 67
pKi ~5.0 (Ki ~1x10-5 M) [67]
GS9667 Hs Agonist <5.0 pKi 28
pKi <5.0 (Ki >1x10-5 M) [28]
Bay60-6583 Hs Agonist <5.0 pKi 59
pKi <5.0 (Ki >1x10-5 M) [59]
MRS3558 Mm Agonist 4.98 pKi 67
pKi 4.98 (Ki 1.04x10-5 M) [67]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]ZM-241385 Rn Antagonist 9.2 pKd 91
pKd 9.2 [91]
[3H]ZM 241385 Hs Antagonist 8.7 – 9.1 pKd 3,37
pKd 8.7 – 9.1 (Kd 8x10-10 – 1.8x10-9 M) [3,37]
[3H]SCH 58261 Hs Antagonist 8.6 – 9.0 pKd 57,89
pKd 8.6 – 9.0 [57,89]
[3H]XAC Hs Antagonist 8.0 pKd 52
pKd 8.0 [52]
SCH442416 Hs Antagonist 8.4 – 10.3 pKi 112,115
pKi 8.4 – 10.3 [112,115]
MRS1093 Hs Antagonist 9.2 pKi 49
pKi 9.2 [49]
preladenant Hs Antagonist 9.05 pKi 79
pKi 9.05 (Ki 9x10-10 M) [79]
ZM-241385 Hs Antagonist 8.8 – 9.1 pKi 89
pKi 8.8 – 9.1 [89]
vipadenant Hs Antagonist 8.89 pKi 39
pKi 8.89 (Ki 1.3x10-9 M) [39]
SCH 58261 Hs Antagonist 8.3 – 9.2 pKi 23,57,89
pKi 8.3 – 9.2 [23,57,89]
XAC Hs Antagonist 8.4 – 9.0 pKi 23,55
pKi 8.4 – 9.0 [23,55]
CGS 15943 Hs Antagonist 7.7 – 9.4 pKi 23,52,55,89
pKi 7.7 – 9.4 [23,52,55,89]
istradefylline Rn Antagonist 8.35 – 8.66 pKi 98,111
pKi 8.35 – 8.66 (Ki 4.46x10-9 – 2.2x10-9 M) [98,111]
ST-1535 Hs Antagonist 8.18 pKi 76
pKi 8.18 (Ki 6.6x10-9 M) [76]
MSX-2 Rn Antagonist 8.09 pKi 80,106
pKi 8.09 (Ki 8.04x10-9 M) [80,106]
MSX-2 Hs Antagonist 7.84 – 8.27 pKi 106
pKi 7.84 – 8.27 (Ki 1.45x10-8 – 5.38x10-9 M) [106]
KF 17837S Hs Antagonist 7.7 pKi 23
pKi 7.7 [23]
istradefylline Hs Antagonist 7.04 – 7.92 pKi 10,32
pKi 7.04 – 7.92 (Ki 9.12x10-8 – 1.2x10-8 M) [10,32]
CSC Rn Antagonist 7.27 pKi 43
pKi 7.27 (Ki 5.4x10-8 M) [43]
DPCPX Hs Antagonist 6.6 – 7.2 pKi 23,55,57,89,127
pKi 6.6 – 7.2 [23,55,57,89,127]
MRE 3008F20 Hs Antagonist 6.8 pKi 44,118-119
pKi 6.8 [44,118-119]
LUF5981 Hs Antagonist 6.71 pKi 10
pKi 6.71 (Ki 1.94x10-7 M) [10]
rolofylline Hs Antagonist 6.2 – 6.97 pKi 50,94
pKi 6.2 – 6.97 (Ki 6.37x10-7 – 1.08x10-7 M) [50,94]
DPCPX Rn Antagonist 6.3 – 6.8 pKi 53,80
pKi 6.3 – 6.8 (Ki 5x10-7 – 1.57x10-7 M) [53,80]
SLV320 Hs Antagonist 6.4 pKi 48
pKi 6.4 (Ki 3.98x10-7 M) [48]
rolofylline Rn Antagonist 6.29 – 6.42 pKi 51,95
pKi 6.29 – 6.42 (Ki 5.1x10-7 – 3.8x10-7 M) [51,95]
KF26777 Hs Antagonist 6.33 pKi 101
pKi 6.33 (Ki 4.7x10-7 M) [101]
MRS1754 Hs Antagonist 6.3 pKi 54
pKi 6.3 (Ki 5.03x10-7 M) [54]
PSB36 Rn Antagonist 6.26 pKi 127
pKi 6.26 (Ki 5.52x10-7 M) [127]
MRS1754 Rn Antagonist 6.21 pKi 54
pKi 6.21 (Ki 6.12x10-7 M) [54]
CPX Hs Antagonist 6.2 pKi 52
pKi 6.2 [52]
ATL802 Hs Antagonist 6.18 pKi 54
pKi 6.18 (Ki 6.54x10-7 M) [54]
CPFPX Rn Antagonist 6.09 pKi 40
pKi 6.09 (Ki 8.12x10-7 M) [40]
CPFPX Hs Antagonist 6.03 pKi 40
pKi 6.03 (Ki 9.4x10-7 M) [40]
PSB36 Hs Antagonist 6.01 pKi 127
pKi 6.01 (Ki 9.8x10-7 M) [127]
galangin Hs Antagonist 6.0 pKi 49
pKi 6.0 [49]
LAS38096 Hs Antagonist <6.0 pKi 25,122
pKi <6.0 (Ki >1x10-6 M) [25,122]
MRE 2029F20 Hs Antagonist <6.0 pKi 4
pKi <6.0 (Ki >1x10-6 M) [4]
FK-453 Hs Antagonist 5.89 pKi 44
pKi 5.89 (Ki 1.3x10-6 M) [44]
PSB-11 Hs Antagonist 5.89 pKi 90
pKi 5.89 (Ki 1.28x10-6 M) [90]
MRS1523 Rn Antagonist 5.69 pKi 67
pKi 5.69 (Ki 2.05x10-6 M) [67]
PSB-11 Rn Antagonist 5.68 pKi 90
pKi 5.68 (Ki 2.1x10-6 M) [90]
tonapofylline Rn Antagonist 5.61 pKi 50
pKi 5.61 (Ki 2.44x10-6 M) [50]
PSB-10 Hs Antagonist 5.57 pKi 90
pKi 5.57 (Ki 2.7x10-6 M) [90]
MRS1041 Hs Antagonist 5.5 pKi 49
pKi 5.5 [49]
flavone Hs Antagonist 5.5 pKi 49
pKi 5.5 [49]
MRS1042 Hs Antagonist 5.5 pKi 49
pKi 5.5 [49]
theophylline Hs Antagonist 5.17 – 5.8 pKi 23,42,55,118
pKi 5.17 – 5.8 [23,42,55,118]
CVT-6883 Hs Antagonist 5.48 pKi 27
pKi 5.48 (Ki 3.28x10-6 M) [27]
MRS1523 Hs Antagonist 5.44 pKi 67
pKi 5.44 (Ki 3.66x10-6 M) [67]
PSB-10 Rn Antagonist 5.22 pKi 82
pKi 5.22 (Ki 6.04x10-6 M) [82]
MRS928 Hs Antagonist 5.2 pKi 49
pKi 5.2 [49]
tonapofylline Hs Antagonist 5.19 pKi 50
pKi 5.19 (Ki 6.41x10-6 M) [50]
caffeine Hs Antagonist 4.6 – 5.6 pKi 1,42,57
pKi 4.6 – 5.6 [1,42,57]
ATL802 Mm Antagonist 5.08 pKi 54
pKi 5.08 (Ki 8.393x10-6 M) [54]
MRS1191 Hs Antagonist <5.0 pKi 67
pKi <5.0 (Ki >1x10-5 M) [67]
MRS1191 Rn Antagonist <5.0 pKi 67
pKi <5.0 (Ki >1x10-5 M) [67]
PSB603 Hs Antagonist <5.0 pKi 7
pKi <5.0 (Ki >1x10-5 M) [7]
PSB603 Rn Antagonist <5.0 pKi 7
pKi <5.0 (Ki >1x10-5 M) [7]
VUF5574 Rn Antagonist >5.0 pKi 116
pKi >5.0 (Ki <1x10-5 M) [116]
MRS1065 Hs Antagonist 4.9 pKi 49
pKi 4.9 [49]
morin Hs Antagonist 4.8 pKi 49
pKi 4.8 [49]
theophylline Rn Antagonist 4.6 – 4.66 pKi 42,81
pKi 4.6 – 4.66 (Ki 2.53x10-5 – 2.2x10-5 M) [42,81]
PSB1115 Rn Antagonist 4.62 pKi 81
pKi 4.62 (Ki 2.4x10-5 M) [81]
MRS1132 Hs Antagonist 4.6 pKi 49
pKi 4.6 [49]
MRS1086 Hs Antagonist 4.6 pKi 49
pKi 4.6 [49]
MRS1066 Hs Antagonist 4.5 pKi 49
pKi 4.5 [49]
caffeine Rn Antagonist 4.32 – 4.49 pKi 19,42,80
pKi 4.32 – 4.49 (Ki 4.8x10-5 – 3.25x10-5 M) [19,42,80]
sakuranetin Hs Antagonist 4.4 pKi 49
pKi 4.4 [49]
visnagin Hs Antagonist 4.4 pKi 49
pKi 4.4 [49]
MRS1088 Hs Antagonist 4.3 pKi 49
pKi 4.3 [49]
MRS1084 Hs Antagonist 4.3 pKi 49
pKi 4.3 [49]
MRS923 Hs Antagonist 4.3 pKi 49
pKi 4.3 [49]
View species-specific antagonist tables
Antagonist Comments
Some istradefylline pKi values are derived from unpublished data (Müller et al.).

The human MSX-2 pKi values are derived either from experiments using recombinant receptors expressed in CHO (the higher pKi) or from native receptors in human brain tissue (the lower pKi).
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  88
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Adenylate cyclase stimulation
Phospholipase C stimulation
Comments:  A2A receptors have also been shown to couple to adenylate cyclase via Golf in the striatum [58]
References:  33
Tissue Distribution
Thymus gland > heart, lung > spleen, leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  93
Brain: caudate nucleus.
Species:  Human
Technique:  Northern blotting.
References:  93
Platelets.
Species:  Human
Technique:  Radioligand binding.
References:  22,117
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  14
Heart, lung > kidney, brain.
Species:  Human
Technique:  Northern blotting.
References:  102
Bone marrow-derived mast cells.
Species:  Mouse
Technique:  in situ hybridisation.
References:  73
Brain: caudate putamen.
Species:  Mouse
Technique:  Autoradiography.
References:  69
Kidney: vascular cells.
Species:  Mouse
Technique:  RNAse protection and RT-PCR.
References:  123
Brain: cerebral cortex.
Species:  Mouse
Technique:  Western blotting.
References:  69
CNS: perikarya and neuropil labelling in regions such as the striatum, nucleus accumbens, olfactory tubercles, extended amygdala, globus pallidus, nucleus of the solitary tract, cortex, hippocampus, thalamus, cerebellum, medulla, pons.
Very high levels of A1 receptor expression in the striatum are important in the regulation of dopamine receptors and Parkinson's desease.
Species:  Rat
Technique:  immunocytochemistry.
References:  100
Brain: hippocampus (mainly in nerve terminals) and striatum (mainly in cell bodies).
Species:  Rat
Technique:  immunocytochemistry.
References:  99
Kidney: vascular cells.
Species:  Rat
Technique:  RNAse protection and RT-PCR.
References:  123
Brain: hippocampus and striatum.
Species:  Rat
Technique:  Radioligand binding.
References:  99
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP levels in human platelets endogenously expressing the A2A receptor.
Species:  Human
Tissue:  Platelets.
Response measured:  cAMP accumulation.
References:  17
Measurement of extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation in CHO cells transfected with the human A1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Phosphorylation of ERK1/2.
References:  109
Measurement of cAMP levels in CHO cells transfected with the human A2A receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation.
References:  8
Measurement of cAMP levels and p42/p44 MAPK phosphorylation in a murine dendritic cell line, XS-106, endogenously expressing the A2A receptor.
Species:  Mouse
Tissue:  XS-206 cells.
Response measured:  Stimulation of cAMP accumulation and p24/p44 MAPK phosphorylation.
References: