A2A receptor

Target id: 19

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.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for A2A receptor in GtoImmuPdb

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 37,64,98
Mouse 7 410 10 Adora2a adenosine A2a receptor 77
Rat 7 410 20p12 Adora2a adenosine A2a receptor 16
Previous and Unofficial Names
RDC8
A2-AR
adenosine receptor A2a
Database Links
Specialist databases
GPCRDB aa2ar_human (Hs), aa2ar_mouse (Mm), aa2ar_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
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:  72
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:  66
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:  65
Natural/Endogenous Ligands
adenosine

Download all structure-activity data for this target as a CSV file

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 48,131
pKd 7.7 – 7.8 (Kd 2.2x10-8 – 1.6x10-8 M) [48,131]
[3H]NECA Hs Full agonist 7.7 pKd 58
pKd 7.7 [58]
apadenoson Hs Agonist 9.3 pKi 97
pKi 9.3 (Ki 5x10-10 M) [97]
(R,S)-PHPNECA Hs Full agonist 8.5 pKi 130
pKi 8.5 [130]
UK-432,097 Hs Agonist 8.3 pKi 134
pKi 8.3 [134]
2-hexynyl-NECA Hs Full agonist 8.2 – 8.3 pKi 26,60,130
pKi 8.2 – 8.3 [26,60,130]
compound 4g [PMID: 22220592] Hs Agonist 8.1 pKi 18
pKi 8.1 (Ki 7.76x10-9 M) [18]
NECA Rn Agonist 8.0 pKi 74
pKi 8.0 (Ki 9.7x10-9 M) [74]
NECA Hs Full agonist 6.9 – 8.7 pKi 9,26,41,55,60,135
pKi 6.9 – 8.7 [9,26,41,55,60,135]
CGS 21680 Rn Agonist 7.7 pKi 71
pKi 7.7 (Ki 1.9x10-8 M) [71]
CGS 21680 Hs Full agonist 6.7 – 8.1 pKi 9,26,41,47,55,58,60,91
pKi 6.7 – 8.1 (Ki 1.99x10-7 – 7.94x10-9 M) [9,26,41,47,55,58,60,91]
2-chloroadenosine Rn Agonist 7.1 pKi 22
pKi 7.1 (Ki 7.6x10-8 M) [22]
CV-1808 Hs Full agonist 7.1 pKi 26,60
pKi 7.1 [26,60]
adenosine Rn Agonist 6.8 pKi 135
pKi 6.8 (Ki 1.5x10-7 M) [135]
2-chloroadenosine Hs Full agonist 6.7 – 6.8 pKi 55,60
pKi 6.7 – 6.8 [55,60]
TCPA Hs Agonist 6.7 pKi 6
pKi 6.7 (Ki 2.1x10-7 M) [6]
(R)-PIA Rn Agonist 6.7 pKi 22
pKi 6.7 (Ki 2.2x10-7 M) [22]
binodenoson Hs Agonist 6.6 pKi 47
pKi 6.6 (Ki 2.7x10-7 M) [47]
regadenoson Hs Agonist 6.5 pKi 47
pKi 6.5 (Ki 2.9x10-7 M) [47]
adenosine Hs Agonist 6.5 pKi 33-34,135
pKi 6.5 (Ki 3.1x10-7 M) [33-34,135]
CGS 24012 Hs Full agonist 6.4 pKi 55
pKi 6.4 [55]
N(6)-cyclohexyladenosine Rn Agonist 6.3 pKi 22
pKi 6.3 (Ki 4.6x10-7 M) [22]
Cl-IB-MECA Rn Agonist 6.3 pKi 71
pKi 6.3 (Ki 4.7x10-7 M) [71]
PENECA Hs Full agonist 6.2 pKi 130
pKi 6.2 [130]
cyclopentyladenosine Hs Full agonist 6.1 pKi 41,47,58
pKi 6.1 [41,47,58]
(R)-PIA Hs Full agonist 6.0 – 6.2 pKi 26,41,55,58,60
pKi 6.0 – 6.2 [26,41,55,58,60]
CCPA Rn Agonist 6.0 pKi 71
pKi 6.0 (Ki 9.5x10-7 M) [71]
cyclopentyladenosine Rn Agonist 6.0 pKi 71
pKi 6.0 (Ki 9.5x10-7 M) [71]
MRS3558 Rn Agonist 6.0 pKi 71
pKi 6.0 (Ki 1.08x10-6 M) [71]
piclidenoson Hs Full agonist 5.6 – 6.3 pKi 47,55,58
pKi 5.6 – 6.3 [47,55,58]
HEMADO Hs Agonist 5.9 pKi 59,130
pKi 5.9 (Ki 1.2x10-6 M) [59,130]
N(6)-cyclohexyladenosine Hs Full agonist 5.9 pKi 26,60
pKi 5.9 [26,60]
GR79236 Hs Agonist 5.9 pKi 47
pKi 5.9 (Ki 1.3x10-6 M) [47]
CV-1674 Hs Full agonist 5.8 pKi 60
pKi 5.8 [60]
tecadenoson Pig Agonist 5.6 pKi 47,84
pKi 5.6 (Ki 2.315x10-6 M) [47,84]
MRS3558 Hs Agonist 5.6 pKi 47
pKi 5.6 (Ki 2.33x10-6 M) [47]
CCPA Hs Full agonist 5.6 pKi 47,58
pKi 5.6 [47,58]
metrifudil Hs Full agonist 5.5 pKi 60
pKi 5.5 [60]
AB-MECA Hs Full agonist 5.4 pKi 58
pKi 5.4 [58]
APNEA Hs Full agonist 5.3 pKi 60
pKi 5.3 [60]
Cl-IB-MECA Hs Agonist 5.3 pKi 47
pKi 5.3 (Ki 5.36x10-6 M) [47]
(S)-PIA Hs Full agonist 5.0 – 5.1 pKi 26,58
pKi 5.0 – 5.1 [26,58]
Cl-IB-MECA Mm Agonist ~5.0 pKi 71
pKi ~5.0 (Ki ~1x10-5 M) [71]
BAY 60-6583 Hs Agonist <5.0 pKi 62
pKi <5.0 (Ki >1x10-5 M) [62]
GS9667 Hs Agonist <5.0 pKi 31
pKi <5.0 (Ki >1x10-5 M) [31]
MRS5151 Hs Agonist <5.0 pKi 79
pKi <5.0 (Ki >1x10-5 M) [79]
MRS5151 Mm Agonist <5.0 pKi 79
pKi <5.0 (Ki >1x10-5 M) [79]
MRS3558 Mm Agonist 5.0 pKi 71
pKi 5.0 (Ki 1.04x10-5 M) [71]
View species-specific agonist tables
Agonist Comments
The INN-assigned compound evodenoson is an agonist of the A2A receptor but affinity data is not available.
Note that for tecadenoson, there is inconsistency between the two referenced articles (from the same group) as to the species origin of the ADORA2A used to generate the Ki value which is presented as identical in both articles. We have used the earlier paper as precedent, which indicates the use of the porcine receptor.
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 96
pKd 9.2 [96]
[3H]ZM 241385 Hs Antagonist 8.7 – 9.1 pKd 4,40
pKd 8.7 – 9.1 (Kd 1.8x10-9 – 8x10-10 M) [4,40]
[3H]SCH 58261 Hs Antagonist 8.6 – 9.0 pKd 60,94
pKd 8.6 – 9.0 [60,94]
[3H]XAC Hs Antagonist 8.0 pKd 55
pKd 8.0 [55]
SCH442416 Hs Antagonist 8.4 – 10.3 pKi 117,120
pKi 8.4 – 10.3 [117,120]
MRS1093 Hs Antagonist 9.2 pKi 52
pKi 9.2 [52]
preladenant Hs Antagonist 9.1 pKi 83
pKi 9.1 (Ki 9x10-10 M) [83]
ZM-241385 Hs Antagonist 8.8 – 9.1 pKi 94
pKi 8.8 – 9.1 [94]
vipadenant Hs Antagonist 8.9 pKi 42
pKi 8.9 (Ki 1.3x10-9 M) [42]
SCH 58261 Hs Antagonist 8.3 – 9.2 pKi 26,60,94
pKi 8.3 – 9.2 [26,60,94]
xanthine amine congener Hs Antagonist 8.4 – 9.0 pKi 26,58
pKi 8.4 – 9.0 [26,58]
CGS 15943 Hs Antagonist 7.7 – 9.4 pKi 26,55,58,94
pKi 7.7 – 9.4 [26,55,58,94]
istradefylline Rn Antagonist 8.4 – 8.7 pKi 103,116
pKi 8.4 – 8.7 (Ki 4.46x10-9 – 2.2x10-9 M) [103,116]
tozadenant Hs Antagonist 8.3 pKi 23
pKi 8.3 (Ki 5x10-9 M) [23]
ST-1535 Hs Antagonist 8.2 pKi 80
pKi 8.2 (Ki 6.6x10-9 M) [80]
MSX-2 Rn Antagonist 8.1 pKi 85,111
pKi 8.1 (Ki 8.04x10-9 M) [85,111]
MSX-2 Hs Antagonist 7.8 – 8.3 pKi 111
pKi 7.8 – 8.3 (Ki 1.45x10-8 – 5.38x10-9 M) [111]
KF 17837S Hs Antagonist 7.7 pKi 26
pKi 7.7 [26]
istradefylline Hs Antagonist 7.0 – 7.9 pKi 11,35
pKi 7.0 – 7.9 (Ki 9.12x10-8 – 1.2x10-8 M) [11,35]
CSC Rn Antagonist 7.3 pKi 46
pKi 7.3 (Ki 5.4x10-8 M) [46]
DPCPX Hs Antagonist 6.6 – 7.2 pKi 26,58,60,94,133
pKi 6.6 – 7.2 [26,58,60,94,133]
MRE 3008F20 Hs Antagonist 6.8 pKi 47,123-124
pKi 6.8 [47,123-124]
LUF5981 Hs Antagonist 6.7 pKi 11
pKi 6.7 (Ki 1.94x10-7 M) [11]
rolofylline Hs Antagonist 6.2 – 7.0 pKi 53,99
pKi 6.2 – 7.0 (Ki 6.37x10-7 – 1.08x10-7 M) [53,99]
DPCPX Rn Antagonist 6.3 – 6.8 pKi 56,85
pKi 6.3 – 6.8 (Ki 5x10-7 – 1.57x10-7 M) [56,85]
derenofylline Hs Antagonist 6.4 pKi 51
pKi 6.4 (Ki 3.98x10-7 M) [51]
rolofylline Rn Antagonist 6.3 – 6.4 pKi 54,100
pKi 6.3 – 6.4 (Ki 5.1x10-7 – 3.8x10-7 M) [54,100]
KF26777 Hs Antagonist 6.3 pKi 106
pKi 6.3 (Ki 4.7x10-7 M) [106]
MRS1754 Hs Antagonist 6.3 pKi 57
pKi 6.3 (Ki 5.03x10-7 M) [57]
PSB36 Rn Antagonist 6.3 pKi 133
pKi 6.3 (Ki 5.52x10-7 M) [133]
MRS1754 Rn Antagonist 6.2 pKi 57
pKi 6.2 (Ki 6.12x10-7 M) [57]
CPX Hs Antagonist 6.2 pKi 55
pKi 6.2 [55]
ATL802 Hs Antagonist 6.2 pKi 57
pKi 6.2 (Ki 6.54x10-7 M) [57]
CPFPX Rn Antagonist 6.1 pKi 43
pKi 6.1 (Ki 8.12x10-7 M) [43]
CPFPX Hs Antagonist 6.0 pKi 43
pKi 6.0 (Ki 9.4x10-7 M) [43]
PSB36 Hs Antagonist 6.0 pKi 133
pKi 6.0 (Ki 9.8x10-7 M) [133]
MRE 2029F20 Hs Antagonist <6.0 pKi 5
pKi <6.0 (Ki >1x10-6 M) [5]
galangin Hs Antagonist 6.0 pKi 52
pKi 6.0 [52]
LAS38096 Hs Antagonist <6.0 pKi 28,128
pKi <6.0 (Ki >1x10-6 M) [28,128]
FK-453 Hs Antagonist 5.9 pKi 47
pKi 5.9 (Ki 1.3x10-6 M) [47]
PSB-11 Hs Antagonist 5.9 pKi 95
pKi 5.9 (Ki 1.28x10-6 M) [95]
MRS1523 Rn Antagonist 5.7 pKi 71
pKi 5.7 (Ki 2.05x10-6 M) [71]
PSB-11 Rn Antagonist 5.7 pKi 95
pKi 5.7 (Ki 2.1x10-6 M) [95]
tonapofylline Rn Antagonist 5.6 pKi 53
pKi 5.6 (Ki 2.44x10-6 M) [53]
PSB-10 Hs Antagonist 5.6 pKi 95
pKi 5.6 (Ki 2.7x10-6 M) [95]
MRS1041 Hs Antagonist 5.5 pKi 52
pKi 5.5 [52]
MRS1042 Hs Antagonist 5.5 pKi 52
pKi 5.5 [52]
flavone Hs Antagonist 5.5 pKi 52
pKi 5.5 [52]
theophylline Hs Antagonist 5.2 – 5.8 pKi 26,45,58,123
pKi 5.2 – 5.8 [26,45,58,123]
CVT-6883 Hs Antagonist 5.5 pKi 30
pKi 5.5 (Ki 3.28x10-6 M) [30]
MRS1523 Hs Antagonist 5.4 pKi 71
pKi 5.4 (Ki 3.66x10-6 M) [71]
PSB-10 Rn Antagonist 5.2 pKi 87
pKi 5.2 (Ki 6.04x10-6 M) [87]
MRS928 Hs Antagonist 5.2 pKi 52
pKi 5.2 [52]
tonapofylline Hs Antagonist 5.2 pKi 53
pKi 5.2 (Ki 6.41x10-6 M) [53]
caffeine Hs Antagonist 4.6 – 5.6 pKi 1,45,60
pKi 4.6 – 5.6 [1,45,60]
ATL802 Mm Antagonist 5.1 pKi 57
pKi 5.1 (Ki 8.393x10-6 M) [57]
MRS1191 Hs Antagonist <5.0 pKi 71
pKi <5.0 (Ki >1x10-5 M) [71]
MRS1191 Rn Antagonist <5.0 pKi 71
pKi <5.0 (Ki >1x10-5 M) [71]
VUF5574 Rn Antagonist >5.0 pKi 121
pKi >5.0 (Ki <1x10-5 M) [121]
PSB603 Hs Antagonist <5.0 pKi 8
pKi <5.0 (Ki >1x10-5 M) [8]
PSB603 Rn Antagonist <5.0 pKi 8
pKi <5.0 (Ki >1x10-5 M) [8]
MRS1065 Hs Antagonist 4.9 pKi 52
pKi 4.9 [52]
morin Hs Antagonist 4.8 pKi 52
pKi 4.8 [52]
theophylline Rn Antagonist 4.6 – 4.7 pKi 45,86
pKi 4.6 – 4.7 (Ki 2.53x10-5 – 2.2x10-5 M) [45,86]
PSB1115 Rn Antagonist 4.6 pKi 86
pKi 4.6 (Ki 2.4x10-5 M) [86]
MRS1086 Hs Antagonist 4.6 pKi 52
pKi 4.6 [52]
MRS1132 Hs Antagonist 4.6 pKi 52
pKi 4.6 [52]
MRS1066 Hs Antagonist 4.5 pKi 52
pKi 4.5 [52]
caffeine Rn Antagonist 4.3 – 4.5 pKi 21,45,85
pKi 4.3 – 4.5 (Ki 4.8x10-5 – 3.25x10-5 M) [21,45,85]
sakuranetin Hs Antagonist 4.4 pKi 52
pKi 4.4 [52]
visnagin Hs Antagonist 4.4 pKi 52
pKi 4.4 [52]
MRS1084 Hs Antagonist 4.3 pKi 52
pKi 4.3 [52]
MRS923 Hs Antagonist 4.3 pKi 52
pKi 4.3 [52]
MRS1088 Hs Antagonist 4.3 pKi 52
pKi 4.3 [52]
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:  93
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 [61]
References:  36
Tissue Distribution
Brain: caudate nucleus.
Species:  Human
Technique:  Northern blotting.
References:  98
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  15
Heart, lung > kidney, brain.
Species:  Human
Technique:  Northern blotting.
References:  107
Platelets.
Species:  Human
Technique:  Radioligand binding.
References:  25,122
Thymus gland > heart, lung > spleen, leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  98
Brain: caudate putamen.
Species:  Mouse
Technique:  Autoradiography.
References:  73
Brain: cerebral cortex.
Species:  Mouse
Technique:  Western blotting.
References:  73
Bone marrow-derived mast cells.
Species:  Mouse
Technique:  in situ hybridisation.
References:  77
Kidney: vascular cells.
Species:  Mouse
Technique:  RNAse protection and RT-PCR.
References:  129
Brain: hippocampus and striatum.
Species:  Rat
Technique:  Radioligand binding.
References:  104