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A3 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 21

Nomenclature: A3 receptor

Family: Adenosine receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 318 1p13.2 ADORA3 adenosine A3 receptor 1,68,78,81
Mouse 7 319 3 46.45 cM Adora3 adenosine A3 receptor 109
Rat 7 320 2q34 Adora3 adenosine A3 receptor 113
Previous and Unofficial Names Click here for help
Adenosine receptor A3 | TGPCR1 | A3AR | ARA3
Database Links Click here for help
Specialist databases
GPCRdb aa3r_human (Hs), aa3r_mouse (Mm), aa3r_rat (Rn)
Other databases
Alphafold P0DMS8 (Hs), Q61618 (Mm), P28647 (Rn)
ChEMBL Target CHEMBL256 (Hs), CHEMBL1075269 (Mm), CHEMBL3360 (Rn)
DrugBank Target P0DMS8 (Hs)
Ensembl Gene ENSG00000282608 (Hs), ENSMUSG00000000562 (Mm), ENSRNOG00000015788 (Rn)
Entrez Gene 140 (Hs), 11542 (Mm), 25370 (Rn)
Human Protein Atlas ENSG00000282608 (Hs)
KEGG Gene hsa:140 (Hs), mmu:11542 (Mm), rno:25370 (Rn)
OMIM 600445 (Hs)
Pharos P0DMS8 (Hs)
RefSeq Nucleotide NM_000677 (Hs), NM_009631 (Mm), NM_012896 (Rn)
RefSeq Protein NP_000668 (Hs), NP_033761 (Mm), NP_037028 (Rn)
UniProtKB P0DMS8 (Hs), Q61618 (Mm), P28647 (Rn)
Wikipedia ADORA3 (Hs)
Natural/Endogenous Ligands Click here for help
adenosine

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]AB-MECA Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.0 – 9.1 pKd 74,97
⤷ pKd 9.0 – 9.1 (Kd 1x10-9 – 6x10-10 M) [74,97]
[3H]HEMADO Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.0 pKd 55
⤷ pKd 9.0 [55]
[125I]AB-MECA Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 8.9 pKd 73
⤷ pKd 8.9 [73]
[3H]NECA Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.9 – 8.2 pKd 26,56
⤷ pKd 7.9 – 8.2 [26,56]
[125I]APNEA Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 7.8 pKd 113
⤷ pKd 7.8 [113]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Mm Agonist 9.7 pKi 61
⤷ pKi 9.7 (Ki 1.8x10-10 M) [61]
MRS3558 Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.5 pKi 46
⤷ pKi 9.5 (Ki 2.9x10-10 M) [46]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Rn Agonist 9.5 pKi 61
⤷ pKi 9.5 (Ki 3.3x10-10 M) [61]
(R,S)-PHPNECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.4 pKi 101
⤷ pKi 9.4 [101]
2-phenylethylyl-adenosine derivative Small molecule or natural product Hs Agonist 9.4 pKi 100
⤷ pKi 9.4 (Ki 4.4x10-10 M) [100]
MRS3558 Small molecule or natural product Click here for species-specific activity table Rn Agonist 9.0 pKi 61
⤷ pKi 9.0 (Ki 1x10-9 M) [61]
HEMADO Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.0 pKi 55,101
⤷ pKi 9.0 (Ki 1.1x10-9 M) [55,101]
piclidenoson Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 8.7 – 9.2 pKi 26,32,56,97
⤷ pKi 8.7 – 9.2 [26,32,56,97]
MRS3558 Small molecule or natural product Click here for species-specific activity table Mm Agonist 8.8 pKi 61
⤷ pKi 8.8 (Ki 1.49x10-9 M) [61]
MRS5151 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.6 pKi 66
⤷ pKi 8.6 (Ki 2.38x10-9 M) [66]
compound 6c [PMID: 34435786] Small molecule or natural product Hs Agonist 8.6 pKi 59
⤷ pKi 8.6 (Ki 2.4x10-9 M) [59]
2-hexynyl-NECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 pKi 101
⤷ pKi 8.6 [101]
MRS5698 Small molecule or natural product Hs Agonist 8.5 pKi 90
⤷ pKi 8.5 [90]
Cl-IB-MECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.0 – 8.9 pKi 10,47,52
⤷ pKi 8.0 – 8.9 [10,47,52]
CP608,039 Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.2 pKi 91
⤷ pKi 8.2 (Ki 5.8x10-9 M) [91]
PENECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 pKi 101
⤷ pKi 8.2 [101]
I-ABA Small molecule or natural product Hs Full agonist 8.0 pKi 81
⤷ pKi 8.0 [81]
MRE 3008F20 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.0 pKi 97
⤷ pKi 8.0 [97]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.5 – 8.4 pKi 9,33,47,81,97,104
⤷ pKi 7.5 – 8.4 [9,33,47,81,97,104]
AB-MECA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.7 pKi 56,97
⤷ pKi 7.7 [56,97]
MRS5151 Small molecule or natural product Click here for species-specific activity table Mm Agonist 7.6 pKi 66
⤷ pKi 7.6 (Ki 2.44x10-8 M) [66]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.1 – 8.1 pKi 33,47,56,81,97
⤷ pKi 7.1 – 8.1 [33,47,56,81,97]
CCPA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 pKi 46,56
⤷ pKi 7.4 [46,56]
apadenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.3 pKi 46
⤷ pKi 7.3 (Ki 4.5x10-8 M) [46]
cyclopentyladenosine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.0 – 7.4 pKi 33,46,56,81
⤷ pKi 7.0 – 7.4 [33,46,56,81]
(S)-PIA Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 – 7.4 pKi 56,81,97
⤷ pKi 6.3 – 7.4 [56,81,97]
MPC-MECA Small molecule or natural product Hs Full agonist 6.8 pKi 97
⤷ pKi 6.8 [97]
NECA Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 6.6 – 6.9 pKi 64,73
⤷ pKi 6.6 – 6.9 [64,73]
N(6)-cyclohexyladenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.8 pKi 92
⤷ pKi 6.8 (Ki 1.76x10-7 M) [92]
(R)-PIA Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.6 – 6.8 pKi 16,73
⤷ pKi 6.6 – 6.8 [16,73]
CCPA Small molecule or natural product Click here for species-specific activity table Rn Agonist 6.6 pKi 61
⤷ pKi 6.6 (Ki 2.37x10-7 M) [61]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 – 7.2 pKi 9,33,46,56,97
⤷ pKi 6.0 – 7.2 [9,33,46,56,97]
adenosine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 6.5 pKi 29-30,104
⤷ pKi 6.5 (Ki 2.9x10-7 M) [29-30,104]
CGS 21680 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 6.2 pKi 61
⤷ pKi 6.2 (Ki 5.84x10-7 M) [61]
TCPA Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.2 pKi 6
⤷ pKi 6.2 (Ki 6x10-7 M) [6]
binodenoson Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.0 pKi 46
⤷ pKi 6.0 (Ki 9.03x10-7 M) [46]
GS9667 Small molecule or natural product Click here for species-specific activity table Hs Agonist <6.0 pKi 22
⤷ pKi <6.0 (Ki >1x10-6 M) [22]
N(6)-cyclohexyladenosine Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.0 pKi 79
⤷ pKi 6.0 (Ki 1.025x10-6 M) [79]
2-chloroadenosine Small molecule or natural product Click here for species-specific activity table Rn Agonist 5.7 pKi 92
⤷ pKi 5.7 (Ki 1.89x10-6 M) [92]
2'-Me-CCPA Small molecule or natural product Rn Agonist 5.3 pKi 28
⤷ pKi 5.3 (Ki 5x10-6 M) [28]
adenosine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Agonist 5.2 pKi 104
⤷ pKi 5.2 (Ki 6.5x10-6 M) [104]
BAY 60-6583 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist <5.0 pKi 57
⤷ pKi <5.0 (Ki >1x10-5 M) [57]
regadenoson Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist <5.0 pKi 46
⤷ pKi <5.0 (Ki >1x10-5 M) [46]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]MRE 3008F20 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.1 pKd 4,97
⤷ pKd 9.1 [4,97]
PSB-11 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKd 69
⤷ pKd 8.3 (Kd 4.9x10-9 M) [69]
[3H]PSB-11 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.3 pKd 69
⤷ pKd 8.3 [69]
KF26777 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.7 pKi 80
⤷ pKi 9.7 (Ki 2x10-10 M) [80]
PSB-10 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.4 pKi 71
⤷ pKi 9.4 (Ki 4.41x10-10 M) [71]
MRE 3010F20 Small molecule or natural product Hs Antagonist 9.3 pKi 97
⤷ pKi 9.3 [97]
MRE 3008F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.0 – 9.5 pKi 46,96-97
⤷ pKi 9.0 – 9.5 [46,96-97]
MRS1220 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 9.2 pKi 47,54,87,107
⤷ pKi 8.2 – 9.2 (Ki 6.31x10-9 – 6.3x10-10 M) [47,54,87,107]
PSB-11 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 75
⤷ pKi 8.6 (Ki 2.34x10-9 M) [75]
MRS1177 Small molecule or natural product Hs Antagonist 8.5 pKi 54
⤷ pKi 8.5 [54]
VUF5574 Small molecule or natural product Hs Antagonist 8.4 pKi 94
⤷ pKi 8.4 (Ki 4.03x10-9 M) [94]
MRS1186 Small molecule or natural product Hs Antagonist 8.1 pKi 54
⤷ pKi 8.1 [54]
MRS1505 Small molecule or natural product Hs Antagonist 8.1 pKi 60
⤷ pKi 8.1 [60]
LUF7602 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 pKi 106
⤷ pKi 8.0 (Ki 1x10-8 M) [106]
Description: Displacement of [3H]PSB-11 binding from the hA3AR (in membranes from stably transfected CHO cells) following preincubation for 4 h,
LJ-4517 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.8 pKi 85
⤷ pKi 7.8 (Ki 1.56x10-8 M) [85]
VUF8504 Small molecule or natural product Hs Antagonist 7.8 pKi 93
⤷ pKi 7.8 [93]
xanthine amine congener Small molecule or natural product Ligand has a PDB structure Rn Antagonist 7.7 pKi 73
⤷ pKi 7.7 [73]
I-ABOPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 pKi 81
⤷ pKi 7.7 [81]
MRS1476 Small molecule or natural product Hs Antagonist 7.7 pKi 60
⤷ pKi 7.7 [60]
MRS1523 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 pKi 60
⤷ pKi 7.7 (Ki 1.99x10-8 M) [60]
MRS1191 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 47-48,61
⤷ pKi 7.5 [47-48,61]
MRS1486 Small molecule or natural product Hs Antagonist 7.5 pKi 60
⤷ pKi 7.5 [60]
CGS 15943 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 7.9 pKi 54,56,74,97
⤷ pKi 7.0 – 7.9 [54,56,74,97]
BW-A1433 Small molecule or natural product Rn Antagonist 7.4 pKi 73
⤷ pKi 7.4 [73]
BW-A1433 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 pKi 81
⤷ pKi 7.3 [81]
xanthine amine congener Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.0 – 7.4 pKi 56,81,97
⤷ pKi 7.0 – 7.4 [56,81,97]
MRS1097 Small molecule or natural product Hs Antagonist 7.0 pKi 47,95
⤷ pKi 7.0 [47,95]
MRS1523 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.9 pKi 61
⤷ pKi 6.9 (Ki 1.13x10-7 M) [61]
VUF8507 Small molecule or natural product Hs Antagonist 6.7 pKi 93
⤷ pKi 6.7 [93]
derenofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 pKi 49
⤷ pKi 6.7 (Ki 2x10-7 M) [49]
MRS1042 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.5 pKi 50
⤷ pKi 6.5 [50]
MRS1041 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 50
⤷ pKi 6.4 [50]
MRS1754 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 53
⤷ pKi 6.2 (Ki 5.7x10-7 M) [53]
MRS1067 Small molecule or natural product Hs Antagonist 6.2 pKi 47,50
⤷ pKi 6.2 [47,50]
LUF5981 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 12
⤷ pKi 6.2 (Ki 6.37x10-7 M) [12]
MRS1523 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 6.1 pKi 61
⤷ pKi 6.1 (Ki 7.31x10-7 M) [61]
ZM-241385 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.1 pKi 46
⤷ pKi 6.1 (Ki 7.43x10-7 M) [46]
MRS1093 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 50
⤷ pKi 6.1 [50]
MRS1088 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 50
⤷ pKi 6.1 [50]
DPCPX Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 – 6.6 pKi 2,39,56,81,97,102
⤷ pKi 5.4 – 6.6 (Ki 3.96x10-6 – 2.43x10-7 M) [2,39,56,81,97,102]
MRE 2029F20 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <6.0 pKi 5
⤷ pKi <6.0 (Ki >1x10-6 M) [5]
vipadenant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 6.0 pKi 35
⤷ pKi 6.0 (Ki 1.005x10-6 M) [35]
ST-1535 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <6.0 pKi 67
⤷ pKi <6.0 (Ki >1x10-6 M) [67]
preladenant Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist <6.0 pKi 70
⤷ pKi <6.0 (Ki >1x10-6 M) [70]
ATL802 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <6.0 pKi 53
⤷ pKi <6.0 (Ki >1x10-6 M) [53]
DPCPX Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.4 – 7.6 pKi 2,73,102
⤷ pKi 4.4 – 7.6 [2,73,102]
LAS38096 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 20,99
⤷ pKi 6.0 (Ki 1.043x10-6 M) [20,99]
CVT-6883 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 21
⤷ pKi 6.0 (Ki 1.07x10-6 M) [21]
SCH 58261 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 46
⤷ pKi 5.9 (Ki 1.2x10-6 M) [46]
MRS928 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.9 pKi 50
⤷ pKi 5.9 [50]
MRS1191 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.8 pKi 60-61
⤷ pKi 5.8 [60-61]
dexniguldipine Small molecule or natural product Hs Antagonist 5.7 pKi 95
⤷ pKi 5.7 [95]
PSB36 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.6 pKi 102
⤷ pKi 5.6 (Ki 2.3x10-6 M) [102]
galangin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.5 pKi 50
⤷ pKi 5.5 [50]
sakuranetin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.5 pKi 50
⤷ pKi 5.5 [50]
nicardipine Small molecule or natural product Approved drug Hs Antagonist 5.5 pKi 95
⤷ pKi 5.5 [95]
rolofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 pKi 51
⤷ pKi 5.4 (Ki 4.39x10-6 M) [51]
istradefylline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.3 pKi 31
⤷ pKi 5.3 (Ki 4.47x10-6 M) [31]
PSB36 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.2 pKi 102
⤷ pKi 5.2 (Ki 6.5x10-6 M) [102]
SCH442416 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 46
⤷ pKi <5.0 (Ki >1x10-5 M) [46]
PSB603 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 8
⤷ pKi <5.0 (Ki >1x10-5 M) [8]
PSB1115 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist <5.0 pKi 39
⤷ pKi <5.0 (Ki >1x10-5 M) [39]
tonapofylline Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 51
⤷ pKi <5.0 (Ki >1x10-5 M) [51]
FK-453 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.0 pKi 46
⤷ pKi 5.0 (Ki 1x10-5 M) [46]
CSC Small molecule or natural product Click here for species-specific activity table Rn Antagonist <5.0 pKi 92
⤷ pKi <5.0 (Ki >1x10-5 M) [92]
MSX-2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <5.0 pKi 83
⤷ pKi <5.0 (Ki >1x10-5 M) [83]
ATL802 Small molecule or natural product Click here for species-specific activity table Mm Antagonist <5.0 pKi 53
⤷ pKi <5.0 (Ki >1x10-5 M) [53]
caffeine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.9 pKi 44
⤷ pKi 4.9 (Ki 1.33x10-5 M) [44]
flavone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.8 pKi 50
⤷ pKi 4.8 [50]
theophylline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 4.1 – 4.7 pKi 44,56
⤷ pKi 4.1 – 4.7 (Ki 8.64x10-5 – 2.23x10-5 M) [44,56]
flavanone Small molecule or natural product Hs Antagonist 4.3 pKi 50
⤷ pKi 4.3 [50]
visnagin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 4.2 pKi 50
⤷ pKi 4.2 [50]
theophylline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Rn Antagonist 4.0 – 4.1 pKi 45,92
⤷ pKi 4.0 – 4.1 (Ki 1x10-4 – 8.5x10-5 M) [45,92]
caffeine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist <4.0 pKi 8
⤷ pKi <4.0 (Ki >1x10-4 M) [8]
View species-specific antagonist tables
Antagonist Comments
Istradefylline pKi values at human receptor subtypes A1, A2B and A3 are derived from unpublished data (Müller et al).
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LUF6000 Small molecule or natural product Hs Positive - - 37
⤷ [37]
LUF6096 Small molecule or natural product Hs Positive - - 40
⤷ [40]
MRS8054 Small molecule or natural product Hs Positive - - 24
⤷ [24]
Immunopharmacology Comments
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [98], suggesting a role in controlling arthritic joint inflammation.
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   type I NK T cell (CL:0000921)
Comment:  A3 receptor is expressed by mouse iNKT cells.
References:  72
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Chemotaxis & migration
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  76,113
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  62,112
Tissue Distribution Click here for help
Liver, lung, placenta.
Species:  Human
Technique:  Northern blotting.
References:  68
CNS: corpus callosum, substantia nigra, thalamus, subthalamic nucleus, spinal cord, hippocampus.
Species:  Human
Technique:  Northern blotting.
References:  1
Adrenal cortex, adrenal medulla > spleen, small intestine.
Species:  Human
Technique:  Northern blotting.
References:  1
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  14
Lung, liver, kidney, heart.
Species:  Human
Technique:  Northern blotting.
References:  78
Liver, lung > brain, aorta.
Species:  Human
Technique:  Northern blotting.
References:  81
Lung mast cells.
Species:  Mouse
Technique:  RT-PCR.
References:  112
Testes: spermatocytes, round spermatids, elongating spermatids > Leydig cells.
Species:  Rat
Technique:  in situ hybridisation.
References:  77
Brain: hippocampus.
Species:  Rat
Technique:  Western blotting.
References:  63
Expression Datasets Click here for help

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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 Click here for help
Measurement of IP3 levels in HEK 293 cells transfected with the human A3 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  PTX-sensitive increase in IP3 level.
References:  62
Measurement of cAMP levels in CHO cells transfected with the human A3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  81
Measurement of cAMP levels in COS cells transfected with the rat A3 receptor.
Species:  Rat
Tissue:  COS cells.
Response measured:  PTX-sensitive inhibition of cAMP accumulation.
References:  113
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:  38,84
Measurement of cAMP levels and p42/p44 MAPK phosphorylation in a murine dendritic cell line, XS-106, which endogenously expresses A3 receptors.
Species:  Mouse
Tissue:  XS-106 cells.
Response measured:  Inhibition of cAMP and stimulation of p42/p44 MAPK phosphorylation.
References:  18
Measurement of PKB activity in cardiomyocytes endogenously expressing the A3 receptor.
Species:  Rat
Tissue:  Cardiomyocytes.
Response measured:  PKB phosphorylation via Gi/o.
References:  34
Cell number count of CHO cells transfected with the human A3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Reduction of cell number.
References:  10
Measurement of eosinophil peroxidase and superoxide anion release from human eosinophils endogenously expressing the human A3 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  Release of of eosinophil peroxidase and superoxide anion .
References:  23
Physiological Functions Click here for help
Mast cell activation.
Species:  Mouse
Tissue:  Lung mast cells.
References:  112
Inhibition of noradrenaline release from peripheral sympathetic nerve terminals.
Species:  Rat
Tissue:  Mesenteric artery.
References:  19
Preconditioning.
Species:  Rat
Tissue:  Heart.
References:  17
Coronary vasodilation.
Species:  Rat
Tissue:  Heart.
References:  41
Protection from reperfusion/reoxygenation injury.
Species:  Rat
Tissue:  Heart.
References:  65
Localised inflammatory response in peripheral tissues.
Species:  Mouse
Tissue:  In vivo (hind paw).
References:  103
Regulation of intraocular pressure.
Species:  Mouse
Tissue:  In vivo (eye).
References:  3
Preconditioning.
Species:  Mouse
Tissue:  Heart.
References:  108
Modulation of synaptic plasticity.
Species:  Rat
Tissue:  Hippocampus.
References:  15
Modulation of ischemia/reperfusion injury.
Species:  Mouse
Tissue:  In vivo.
References:  11,36
Hypotension.
Species:  Rat
Tissue:  In vivo.
References:  86
Mast cell degranulation.
Species:  Rat
Tissue:  Mast cells.
References:  27
Physiological Consequences of Altering Gene Expression Click here for help
A3 knockout mice exhibit no potentiation of antigen-dependent degranulation of bone marrow-derived mast cells, as with the wild-type mice, and decreased inhibition of TNFα production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  82
A3 receptor knockout mice exhibit decreased adenosine-induced airway responsiveness.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  88
A3 receptor knockout mice exhibit protection from ischemic or myoglobinuric renal failure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  58
A3 receptor knockout mice exhibit defective localised inflammatory responses.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  103
A3 receptor knockout mice exhibit reduced intraocular pressure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  3
Overexpression of the A3 receptor gene by the SM22 alpha promoter resulted in lethality at an early stage of embryo development.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  111
A3 receptor knockout mice exhibit resistance to cardiac ischemia-reperfusion injury.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11,36
A3 receptor knockout mice exhibit increased cAMP levels in the heart and vascular smooth muscle, as well as a decrease in blood pressure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  110
A3 receptor knockout mice exhibit defective cutaneous vascular permeability.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  89
A3 receptor knockout mice exhibit great carbon monoxide-induced neuronal damage, slightly increased locomotor activity and altered response to painful stimuli.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  25
Adenosine A3 receptor KO mice exhibit a 20% decrease of their blood platelet count.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  42
Neutrophils lacking A3 receptors show decreased chemotaxis
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
Adenosine A3 receptor KO mice show changes in diurnal rhythm and temperature regulation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  105
Adenosine A3 receptor KO male mice show an increase in overall motor activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7
A3 KO mice show decreased mast cell activation
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  43
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adora3tm1Jbsn Adora3tm1Jbsn/Adora3tm1Jbsn
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * C57BL/6)		 MGI:104847  MP:0002423 abnormal mast cell physiology PMID: 10660615 
Adora3tm1Jbsn Adora3tm1Jbsn/Adora3tm1Jbsn
either: (involves: 129P2/OlaHsd * C57BL/6 * DBA/2) or (involves: 129P2/OlaHsd * C57BL/6)		 MGI:104847  MP:0008561 decreased tumor necrosis factor secretion PMID: 10660615 
General Comments
For a review of the effects of adenosine receptor knockout on nervous system function see reference [30].

References

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2. Auchampach JA, Jin X, Wan TC, Caughey GH, Linden J. (1997) Canine mast cell adenosine receptors: cloning and expression of the A3 receptor and evidence that degranulation is mediated by the A2B receptor. Mol Pharmacol, 52 (5): 846-60. [PMID:9351976]

3. Avila MY, Stone RA, Civan MM. (2002) Knockout of A3 adenosine receptors reduces mouse intraocular pressure. Invest Ophthalmol Vis Sci, 43 (9): 3021-6. [PMID:12202525]

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6. Beukers MW, Wanner MJ, Von Frijtag Drabbe Künzel JK, Klaasse EC, IJzerman AP, Koomen GJ. (2003) N6-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA), a very selective agonist with high affinity for the human adenosine A1 receptor. J Med Chem, 46 (8): 1492-503. [PMID:12672250]

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12. Chang LC, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, Westerhout J, Spangenberg T, Brussee J, Ijzerman AP. (2007) 2,6,8-trisubstituted 1-deazapurines as adenosine receptor antagonists. J Med Chem, 50 (4): 828-34. [PMID:17300165]

13. Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG. (2006) ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science, 314 (5806): 1792-5. [PMID:17170310]

14. Christofi FL, Zhang H, Yu JG, Guzman J, Xue J, Kim M, Wang YZ, Cooke HJ. (2001) Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the human enteric nervous system. J Comp Neurol, 439 (1): 46-64. [PMID:11579381]

15. Costenla AR, Lopes LV, de Mendonça A, Ribeiro JA. (2001) A functional role for adenosine A3 receptors: modulation of synaptic plasticity in the rat hippocampus. Neurosci Lett, 302 (1): 53-7. [PMID:11278110]

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17. Das S, Cordis GA, Maulik N, Das DK. (2005) Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol Heart Circ Physiol, 288 (1): H328-35. [PMID:15345477]

18. Dickenson JM, Reeder S, Rees B, Alexander S, Kendall D. (2003) Functional expression of adenosine A2A and A3 receptors in the mouse dendritic cell line XS-106. Eur J Pharmacol, 474 (1): 43-51. [PMID:12909194]

19. Donoso MV, Aedo F, Huidobro-Toro JP. (2006) The role of adenosine A2A and A3 receptors on the differential modulation of norepinephrine and neuropeptide Y release from peripheral sympathetic nerve terminals. J Neurochem, 96 (6): 1680-95. [PMID:16539684]

20. Eastwood P, Gonzalez J, Paredes S, Nueda A, Domenech T, Alberti J, Vidal B. (2010) Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective A(2B) adenosine receptor antagonists. Bioorg Med Chem Lett, 20 (5): 1697-700. [PMID:20137946]

21. Elzein E, Kalla RV, Li X, Perry T, Gimbel A, Zeng D, Lustig D, Leung K, Zablocki J. (2008) Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate for chronic inflammatory airway diseases. J Med Chem, 51 (7): 2267-78. [PMID:18321039]

22. Elzein E, Zablocki J. (2008) A1 adenosine receptor agonists and their potential therapeutic applications. Expert Opin Investig Drugs, 17 (12): 1901-10. [PMID:19012505]

23. Ezeamuzie CI, Philips E. (1999) Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. Br J Pharmacol, 127 (1): 188-94. [PMID:10369472]

24. Fallot LB, Suresh RR, Fisher CL, Salmaso V, O'Connor RD, Kaufman N, Gao ZG, Auchampach JA, Jacobson KA. (2022) Structure-Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A3 Adenosine Receptor Positive Allosteric Modulators. J Med Chem, 65 (22): 15238-15262. [PMID:36367749]

25. Fedorova IM, Jacobson MA, Basile A, Jacobson KA. (2003) Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol, 23 (3): 431-47. [PMID:12825837]

26. Feoktistov I, Garland EM, Goldstein AE, Zeng D, Belardinelli L, Wells JN, Biaggioni I. (2001) Inhibition of human mast cell activation with the novel selective adenosine A(2B) receptor antagonist 3-isobutyl-8-pyrrolidinoxanthine (IPDX)(2). Biochem Pharmacol, 62 (9): 1163-73. [PMID:11705449]

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34. Germack R, Griffin M, Dickenson JM. (2004) Activation of protein kinase B by adenosine A1 and A3 receptors in newborn rat cardiomyocytes. J Mol Cell Cardiol, 37 (5): 989-99. [PMID:15522276]

35. Gillespie RJ, Bamford SJ, Botting R, Comer M, Denny S, Gaur S, Griffin M, Jordan AM, Knight AR, Lerpiniere J et al.. (2009) Antagonists of the human A(2A) adenosine receptor. 4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines. J Med Chem, 52 (1): 33-47. [PMID:19072055]

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37. Göblyös A, Gao ZG, Brussee J, Connestari R, Santiago SN, Ye K, Ijzerman AP, Jacobson KA. (2006) Structure-activity relationships of new 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric enhancers of the A3 adenosine receptor. J Med Chem, 49 (11): 3354-61. [PMID:16722654]

38. Hammarberg C, Fredholm BB, Schulte G. (2004) Adenosine A3 receptor-mediated regulation of p38 and extracellular-regulated kinase ERK1/2 via phosphatidylinositol-3'-kinase. Biochem Pharmacol, 67: 129-134. [PMID:14667935]

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