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A3

Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 318 1p13.2 ADORA3 33,153-155
Rat 7 320 2q34 Adora3 152
Mouse 7 319 3 F2.3 Adora3 156
Contents:
Structural Information
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Receptor Comments
Database Links
ChEMBL Target 280 (Hs), 12171 (Rn)
Ensembl ENSG00000121933 (Hs), ENSMUSG00000000562 (Mm), ENSMUSG00000074344 (Mm), ENSRNOG00000015788 (Rn)
Entrez Gene 140 (Hs), 11542 (Mm), 25370 (Rn)
GeneCards ADORA3 (Hs)
HomoloGene 550 (Hs)
OMIM 600445 (Hs)
PharmGKB Gene PA24589 (Hs)
Protein Ontology (PRO) PRO:000001578 (Hs)
RefSeq Nucleotide NM_000677 (Hs), NM_009631 (Mm), NM_012896 (Rn)
RefSeq Protein NP_000668 (Hs), NP_033761 (Mm), NP_037028 (Rn)
UniGene Hs. 281342 (Hs)
UniProt P33765 (Hs), Q61618 (Mm), P28647 (Rn)
Wikipedia A3
Search for 3D structures on the PDB
Search using keywords: Adenosine receptors A3 Search using accession numbers: P28647 || P33765 || Q61618
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
adenosine ? Agonist - - 9,188
[125I]AB-MECA Hs Full agonist 9.1 pKd 82
[3H]AB-MECA Hs Full agonist 9.0 pKd 80
[3H]AB-MECA Rn Full agonist 8.9 pKd 179
[3H]NECA Hs Full agonist 7.9 – 8.2 pKd 76,84
[3H]APNEA Hs Full agonist 7.8 pKd 152
(R,S)-PHPNECA Hs Full agonist 9.4 pKi 70
IB-MECA Hs Full agonist 9.2 pKi 76
IB-MECA Hs Full agonist 8.7 – 8.9 pKi 76,82,84
2-hexynyl-NECA Hs Full agonist 8.6 pKi 70
Cl-IB-MECA Hs Full agonist 8.0 – 8.9 pKi 171,180
PENECA Hs Full agonist 8.2 pKi 70
I-ABA Hs Full agonist 8.0 pKi 33
MRE 3008F20 Hs Full agonist 8.0 pKi 82
NECA Hs Full agonist 7.5 – 8.4 pKi 33,73,82,107,180
AB-MECA Hs Full agonist 7.7 pKi 76,82
(R)-PIA Hs Full agonist 7.1 – 8.1 pKi 33,73,76,82,180
CCPA Hs Full agonist 7.4 pKi 76
cyclopentyladenosine Hs Full agonist 7.0 – 7.4 pKi 33,73,76
(S)-PIA Hs Full agonist 6.3 – 7.4 pKi 33,76,82
MPC-MECA Hs Full agonist 6.8 pKi 82
CGS 21680 Hs Full agonist 6.0 – 7.2 pKi 73,76,82,107
NECA Rn Full agonist 6.6 pKi 179
(R)-PIA Rn Full agonist 6.6 pKi 179
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
[3H]MRE 3008F20 Hs Antagonist 9.1 pKd 82,186
MRE 3010F20 Hs Antagonist 9.3 pKi 82
MRE 3008F20 Hs Antagonist 9.0 – 9.5 pKi 79,82
MRS1220 Hs Antagonist 9.2 pKi 180,182
MRS1177 Hs Antagonist 8.5 pKi 182
MRS1186 Hs Antagonist 8.1 pKi 182
MRS1505 Hs Antagonist 8.1 pKi 184
VUF8504 Hs Antagonist 7.8 pKi 185
I-ABOPX Hs Antagonist 7.7 pKi 33
MRS1476 Hs Antagonist 7.7 pKi 184
MRS1523 Hs Antagonist 7.7 pKi 184
XAC Rn Antagonist 7.7 pKi 179
DPCPX Rn Antagonist 7.6 pKi 179
MRS1191 Hs Antagonist 7.5 pKi 180,183
MRS1486 Hs Antagonist 7.5 pKi 184
CGS 15943 Hs Antagonist 7.0 – 7.9 pKi 76,80,82,182
BW-A1433 Rn Antagonist 7.4 pKi 179
BW-A1433 Hs Antagonist 7.3 pKi 33
XAC Hs Antagonist 7.0 – 7.4 pKi 33,76,82
MRS1097 Hs Antagonist 7.0 pKi 180-181
MRS1523 Hs Antagonist 7.0 pKi 184
VUF8507 Hs Antagonist 6.7 pKi 185
MRS1042 Hs Antagonist 6.5 pKi 83
MRS1041 Hs Antagonist 6.4 pKi 83
MRS1067 Hs Antagonist 6.2 pKi 83,180
MRS1088 Hs Antagonist 6.1 pKi 83
MRS1093 Hs Antagonist 6.1 pKi 83
MRS928 Hs Antagonist 5.9 pKi 83
MRS1191 Rn Antagonist 5.8 pKi 184
DPCPX Hs Antagonist 5.4 – 6.1 pKi 33,76,82
(R)-niguldipine Hs Antagonist 5.7 pKi 181
galangin Hs Antagonist 5.5 pKi 83
nicardipine Hs Antagonist 5.5 pKi 181
sakuranetin Hs Antagonist 5.5 pKi 83
flavone Hs Antagonist 4.8 pKi 83
flavanone Hs Antagonist 4.3 pKi 83
visnagin Hs Antagonist 4.2 pKi 83
theophylline Hs Antagonist 4.1 pKi 76
View species-specific antagonist tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  152,157
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  138,158
Tissue Distribution
Liver, lung > brain, aorta.
Species:  Human
Technique:  Northern blotting.
References:  33
CNS: corpus callosum, substantia nigra, thalamus, subthalamic nucleus, spinal cord, hippocampus.
Species:  Human
Technique:  Northern blotting.
References:  155
Adrenal cortex, adrenal medulla > spleen, small intestine.
Species:  Human
Technique:  Northern blotting.
References:  155
Testes: spermatocytes, round spermatids, elongating spermatids > Leydig cells.
Species:  Rat
Technique:  in situ hybridisation.
References:  36
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  40
Lung mast cells.
Species:  Mouse
Technique:  RT-PCR.
References:  158
Brain: hippocampus.
Species:  Rat
Technique:  Western blotting.
References:  173
Lung, liver, kidney, heart.
Species:  Human
Technique:  Northern blotting.
References:  153
Liver, lung, placenta.
Species:  Human
Technique:  Northern blotting.
References:  154
Functional Assays
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:  138
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:  33
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:  152
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:  31,170
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:  108
Measurement of PKB activity in cardiomyocytes endogenously expressing the A3 receptor.
Species:  Rat
Tissue:  Cardiomyocytes.
Response measured:  PKB phosphorylation via Gi/o.
References:  32
Cell number count of CHO cells transfected with the human A3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Reduction of cell number.
References:  171
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:  172
Physiological Functions
Mast cell activation.
Species:  Mouse
Tissue:  Lung mast cells.
References:  158
Inhibition of noradrenaline release from peripheral sympathetic nerve terminals.
Species:  Rat
Tissue:  Mesenteric artery.
References:  128
Preconditioning.
Species:  Rat
Tissue:  Heart.
References:  174
Coronary vasodilation.
Species:  Rat
Tissue:  Heart.
References:  147
Protection from reperfusion/reoxygenation injury.
Species:  Rat
Tissue:  Heart.
References:  129
Localised inflammatory response in peripheral tissues.
Species:  Mouse
Tissue:  In vivo (hind paw).
References:  162
Regulation of intraocular pressure.
Species:  Mouse
Tissue:  In vivo (eye).
References:  163
Preconditioning.
Species:  Mouse
Tissue:  Heart.
References:  175
Modulation of synaptic plasticity.
Species:  Rat
Tissue:  Hippocampus.
References:  176
Modulation of ischemia/reperfusion injury.
Species:  Mouse
Tissue:  In vivo.
References:  165-166
Hypotension.
Species:  Rat
Tissue:  In vivo.
References:  177
Mast cell degranulation.
Species:  Rat
Tissue:  Mast cells.
References:  178
Physiological Consequences of Altering Gene Expression
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:  159
A3 receptor knockout mice exhibit decreased adenosine-induced airway responsiveness.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  160
A3 receptor knockout mice exhibit protection from ischemic or myoglobinuric renal failure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  161
A3 receptor knockout mice exhibit defective localised inflammatory responses.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  162
A3 receptor knockout mice exhibit reduced intraocular pressure.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  163
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:  164
A3 receptor knockout mice exhibit resistance to cardiac ischemia-reperfusion injury.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  165-166
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:  167
A3 receptor knockout mice exhibit defective cutaneous vascular permeability.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  168
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:  169
Receptor Comments
For a review of the effects of adenosine receptor knockout on nervous system function see reference [9].

To cite this receptor data page, please use the following:

Bertil B. Fredholm, Bruno G. Frenguelli, Rebecca Hills, Adriaan P. Ijzerman, Kenneth A. Jacobson, Joel Linden, Ulrich Schwabe, Gary L. Stiles.
Adenosine receptors: A3. Last modified on 2010-08-24. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=21.


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