A1 receptor

Target id: 18

Nomenclature: A1 receptor

Family: Adenosine receptors

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Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 326 1q32.1 ADORA1 adenosine A1 receptor 78,107,130
Mouse 7 326 1 E4 Adora1 adenosine A1 receptor 86,139
Rat 7 326 13q13 Adora1 adenosine A1 receptor 85
Previous and Unofficial Names
RDC7
adenosine receptor A1
A1-AR
A1R
Database Links
Specialist databases
GPCRDB aa1r_human (Hs), aa1r_mouse (Mm), aa1r_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NeXtProt
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
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]CCPA Hs Full agonist 9.2 pKd 69,110
pKd 9.2 (Kd 6.31x10-10 M) [69,110]
5-Cl-5-deoxy-(±)-ENBA Hs Full agonist 9.3 pKi 30
pKi 9.3 (Ki 5.1x10-10 M) [30]
N(6)-cyclohexyladenosine Rn Agonist 9.1 pKi 19
pKi 9.1 (Ki 8.5x10-10 M) [19]
(R)-PIA Rn Agonist 8.9 pKi 19
pKi 8.9 (Ki 1.2x10-9 M) [19]
CCPA Rn Agonist 8.9 pKi 77
pKi 8.9 (Ki 1.3x10-9 M) [77]
(R,S)-PHPNECA Hs Full agonist 8.6 pKi 137
pKi 8.6 [137]
TCPA Hs Agonist 8.6 pKi 7
pKi 8.6 (Ki 2.8x10-9 M) [7]
GR79236 Rn Agonist 8.5 pKi 55
pKi 8.5 (Ki 3.1x10-9 M) [55]
NECA Rn Agonist 8.3 pKi 81
pKi 8.3 (Ki 5.1x10-9 M) [81]
tecadenoson Pig Agonist 8.2 pKi 55,95
pKi 8.2 (Ki 6.5x10-9 M) [55,95]
2-chloroadenosine Rn Agonist 8.2 pKi 19
pKi 8.2 (Ki 6.7x10-9 M) [19]
cyclopentyladenosine Hs Full agonist 6.5 – 9.4 pKi 17,20,35,46,55-56,110
pKi 6.5 – 9.4 [17,20,35,46,55-56,110]
CCPA Hs Full agonist 7.7 – 8.1 pKi 55,99
pKi 7.7 – 8.1 [55,99]
MRS3558 Mm Agonist 7.8 pKi 77
pKi 7.8 (Ki 1.58x10-8 M) [77]
LUF5831 Hs Partial agonist 7.7 pKi 46
pKi 7.7 [46]
(R)-PIA Hs Full agonist 6.4 – 8.7 pKi 35,56,69,110,129
pKi 6.4 – 8.7 [35,56,69,110,129]
Cl-IB-MECA Mm Agonist 7.5 pKi 77
pKi 7.5 (Ki 3.5x10-8 M) [77]
piclidenoson Hs Agonist 7.3 pKi 55
pKi 7.3 (Ki 5.1x10-8 M) [55]
GS9667 Hs Agonist 7.3 pKi 28
pKi 7.3 (Ki 5.5x10-8 M) [28]
2-hexynyl-NECA Hs Full agonist 7.2 pKi 137
pKi 7.2 [137]
adenosine Rn Agonist 7.1 pKi 142
pKi 7.1 (Ki 7.3x10-8 M) [142]
apadenoson Hs Agonist 7.1 pKi 55
pKi 7.1 (Ki 7.7x10-8 M) [55]
adenosine Hs Agonist ~7.0 pKi 142
pKi ~7.0 (Ki ~1x10-7 M) [142]
MRS3558 Rn Agonist 7.0 pKi 77
pKi 7.0 (Ki 1.05x10-7 M) [77]
NECA Hs Full agonist 5.3 – 8.2 pKi 35,56,110,129,142
pKi 5.3 – 8.2 [35,56,110,129,142]
Cl-IB-MECA Hs Agonist 6.7 pKi 55
pKi 6.7 (Ki 2.2x10-7 M) [55]
MRS3558 Hs Agonist 6.6 pKi 55
pKi 6.6 (Ki 2.6x10-7 M) [55]
Cl-IB-MECA Rn Agonist 6.6 pKi 77
pKi 6.6 (Ki 2.8x10-7 M) [77]
HEMADO Hs Agonist 6.5 pKi 70,137
pKi 6.5 (Ki 3.3x10-7 M) [70,137]
PENECA Hs Full agonist 6.2 pKi 137
pKi 6.2 [137]
CGS 21680 Hs Full agonist 5.8 – 6.4 pKi 35,55
pKi 5.8 – 6.4 [35,55]
CGS 21680 Rn Agonist 5.7 pKi 77
pKi 5.7 (Ki 1.8x10-6 M) [77]
2-chloroadenosine Hs Full agonist 5.2 – 5.6 pKi 56,110
pKi 5.2 – 5.6 [56,110]
(S)-PIA Hs Full agonist 4.6 – 6.0 pKi 56,129
pKi 4.6 – 6.0 [56,129]
CP608,039 Hs Agonist 5.1 pKi 55
pKi 5.1 (Ki 7.3x10-6 M) [55]
BAY 60-6583 Hs Agonist <5.0 pKi 73
pKi <5.0 (Ki >1x10-5 M) [73]
regadenoson Hs Agonist <5.0 pKi 55
pKi <5.0 (Ki >1x10-5 M) [55]
MRS5151 Mm Agonist 5.0 pKi 89
pKi 5.0 (Ki 1.05x10-5 M) [89]
MRS5151 Hs Agonist 4.8 pKi 89
pKi 4.8 (Ki 1.49x10-5 M) [89]
binodenoson Hs Agonist 4.3 pKi 55
pKi 4.3 (Ki 4.8x10-5 M) [55]
View species-specific agonist tables
Agonist Comments
The role for adenosine as endogenous ligand for the A1 receptor is described in [31] and [32].

Tecadenoson (CV-510) is a selective A1 agonist with potential therapeutic use in controlling paroxysmal supraventricular tachycardia [103].
Primary target mapping: we have tagged the adenosine A1 receptor as the primary target for this endogenous ligand as the affinity is marginally higher at this receptor isoform. However, adenosine is likely to exert clinical effects via other adenosine receptor family members.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]DPCPX Hs Antagonist 8.4 – 9.2 pKd 17,29,69,101,110,129
pKd 8.4 – 9.2 (Kd 6x10-10 – 1.2x10-9 M) [17,29,69,101,110,129]
xanthine amine congener Hs Antagonist 7.5 pKd 30
pKd 7.5 [30]
PSB36 Rn Antagonist 9.9 pKi 1
pKi 9.9 (Ki 1.24x10-10 M) [1]
DPCPX Rn Antagonist 9.0 – 9.7 pKi 66,71,138
pKi 9.0 – 9.7 (Ki 1x10-9 – 1.8x10-10 M) [66,71,138]
CPFPX Rn Antagonist 9.2 pKi 49
pKi 9.2 (Ki 6.3x10-10 M) [49]
LUF5981 Hs Antagonist 9.1 pKi 13
pKi 9.1 (Ki 9x10-10 M) [13]
derenofylline Hs Antagonist 9.0 pKi 60
pKi 9.0 (Ki 1x10-9 M) [60]
FR194921 Hs Antagonist 8.9 pKi 84
pKi 8.9 [84]
CPFPX Hs Antagonist 8.9 pKi 49
pKi 8.9 (Ki 1.26x10-9 M) [49]
tonapofylline Rn Antagonist 8.9 pKi 65
pKi 8.9 (Ki 1.3x10-9 M) [65]
rolofylline Rn Antagonist 7.9 – 9.7 pKi 105
pKi 7.9 – 9.7 (Ki 1.26x10-8 – 1.9x10-10 M) [105]
WRC-0571 Hs Antagonist 8.8 pKi 87
pKi 8.8 [87]
rolofylline Hs Antagonist 8.1 – 9.1 pKi 65,105
pKi 8.1 – 9.1 (Ki 8x10-9 – 7.2x10-10 M) [65,105]
derenofylline Rn Antagonist 8.6 pKi 60
pKi 8.6 (Ki 2.51x10-9 M) [60]
CGS 15943 Hs Antagonist 8.5 pKi 101
pKi 8.5 (Ki 3.5x10-9 M) [101]
DPCPX Hs Antagonist 7.4 – 9.2 pKi 20,52,99,110,138
pKi 7.4 – 9.2 (Ki 3.98x10-8 – 6.3x10-10 M) [20,52,99,110,138]
CGS 15943 Rn Antagonist 8.2 pKi 80
pKi 8.2 (Ki 6.4x10-9 M) [80]
tonapofylline Hs Antagonist 8.1 pKi 65
pKi 8.1 (Ki 7.4x10-9 M) [65]
MRS1754 Rn Antagonist 7.8 pKi 67
pKi 7.8 (Ki 1.68x10-8 M) [67]
8-cyclopentyltheophylline Hs Antagonist 7.5 – 8.0 pKi 17
pKi 7.5 – 8.0 [17]
FK-453 Hs Antagonist 7.7 pKi 55
pKi 7.7 (Ki 1.8x10-8 M) [55]
xanthine amine congener Hs Antagonist 7.6 pKi 56
pKi 7.6 [56]
vipadenant Hs Antagonist 7.2 pKi 40
pKi 7.2 (Ki 6.8x10-8 M) [40]
ST-1535 Hs Antagonist 7.1 pKi 92
pKi 7.1 (Ki 7.18x10-8 M) [92]
MRE 2029F20 Hs Antagonist 6.7 pKi 6,133
pKi 6.7 [6,133]
istradefylline Rn Antagonist 6.6 pKi 33
pKi 6.6 (Ki 2.3x10-7 M) [33]
AS70 Hs Antagonist 6.6 pKi 133
pKi 6.6 [133]
AS100 Hs Antagonist 6.5 pKi 133
pKi 6.5 [133]
ATL802 Hs Antagonist 6.4 pKi 67
pKi 6.4 (Ki 3.69x10-7 M) [67]
MRS1754 Hs Antagonist 6.4 pKi 67
pKi 6.4 (Ki 4.03x10-7 M) [67]
PSB-11 Rn Antagonist 6.4 pKi 102
pKi 6.4 (Ki 4.4x10-7 M) [102]
ZM-241385 Hs Antagonist 6.1 – 6.6 pKi 55,101
pKi 6.1 – 6.6 [55,101]
MRS928 Rn Antagonist 6.3 pKi 64
pKi 6.3 [64]
L-97-1 Hs Antagonist 6.2 pKi 99
pKi 6.2 [99]
MRS1041 Rn Antagonist 6.2 pKi 64
pKi 6.2 [64]
SCH 58261 Hs Antagonist 6.1 – 6.3 pKi 55,101,129
pKi 6.1 – 6.3 [55,101,129]
AS99 Hs Antagonist 6.1 pKi 133
pKi 6.1 [133]
galangin Rn Antagonist 6.1 pKi 64
pKi 6.1 [64]
PSB-10 Rn Antagonist 6.1 pKi 97
pKi 6.1 (Ki 8.05x10-7 M) [97]
istradefylline Hs Antagonist 6.1 pKi 33
pKi 6.1 (Ki 8.41x10-7 M) [33]
MSX-2 Rn Antagonist 6.1 pKi 115
pKi 6.1 (Ki 9x10-7 M) [115]
MRS1042 Rn Antagonist 6.0 pKi 64
pKi 6.0 [64]
preladenant Hs Antagonist <6.0 pKi 94
pKi <6.0 (Ki >1x10-6 M) [94]
MRE 3008F20 Hs Antagonist 5.9 – 6.0 pKi 55,133-134
pKi 5.9 – 6.0 [55,133-134]
SCH442416 Hs Antagonist 5.9 pKi 55
pKi 5.9 (Ki 1.11x10-6 M) [55]
PSB-11 Hs Antagonist 5.8 pKi 102
pKi 5.8 (Ki 1.64x10-6 M) [102]
PSB-10 Hs Antagonist 5.8 pKi 102
pKi 5.8 (Ki 1.7x10-6 M) [102]
KF26777 Hs Antagonist 5.7 pKi 111
pKi 5.7 (Ki 1.8x10-6 M) [111]
CVT-6883 Hs Antagonist 5.7 pKi 27
pKi 5.7 (Ki 1.94x10-6 M) [27]
MRS1093 Rn Antagonist 5.7 pKi 64
pKi 5.7 [64]
PSB1115 Rn Antagonist 5.7 pKi 96
pKi 5.7 (Ki 2.2x10-6 M) [96]
MRS1132 Rn Antagonist 5.6 pKi 64
pKi 5.6 [64]
MSX-2 Hs Antagonist 5.6 pKi 115
pKi 5.6 (Ki 2.5x10-6 M) [115]
LAS38096 Hs Antagonist 5.6 pKi 26,135
pKi 5.6 (Ki 2.821x10-6 M) [26,135]
flavone Rn Antagonist 5.5 pKi 64
pKi 5.5 [64]
isobutylmethylxanthine Hs Antagonist 5.1 pKi 56
pKi 5.1 [56]
sakuranetin Rn Antagonist 5.1 pKi 64
pKi 5.1 [64]
theophylline Hs Antagonist 4.9 – 5.2 pKi 29,56,69,133
pKi 4.9 – 5.2 [29,56,69,133]
ATL802 Mm Antagonist 5.0 pKi 67
pKi 5.0 (Ki 9.583x10-6 M) [67]
MRS1191 Hs Antagonist <5.0 pKi 77
pKi <5.0 (Ki >1x10-5 M) [77]
MRS1523 Hs Antagonist <5.0 pKi 77
pKi <5.0 (Ki >1x10-5 M) [77]
VUF5574 Rn Antagonist >5.0 pKi 132
pKi >5.0 (Ki <1x10-5 M) [132]
PSB603 Hs Antagonist <5.0 pKi 10
pKi <5.0 (Ki >1x10-5 M) [10]
PSB603 Rn Antagonist <5.0 pKi 10
pKi <5.0 (Ki >1x10-5 M) [10]
PSB1115 Hs Antagonist <5.0 pKi 45
pKi <5.0 (Ki >1x10-5 M) [45]
theophylline Rn Antagonist 4.8 – 5.1 pKi 53,96
pKi 4.8 – 5.1 (Ki 1.4x10-5 – 8.74x10-6 M) [53,96]
morin Rn Antagonist 4.9 pKi 64
pKi 4.9 [64]
MRS1523 Rn Antagonist 4.8 pKi 77
pKi 4.8 (Ki 1.56x10-5 M) [77]
caffeine Hs Antagonist 4.3 – 5.0 pKi 1,22,53
pKi 4.3 – 5.0 (Ki 4.49x10-5 – 1.07x10-5 M) [1,22,53]
MRS923 Rn Antagonist 4.6 pKi 64
pKi 4.6 [64]
CSC Rn Antagonist 4.6 pKi 54
pKi 4.6 (Ki 2.8x10-5 M) [54]
MRS1065 Rn Antagonist 4.5 pKi 64
pKi 4.5 [64]
MRS1086 Rn Antagonist 4.5 pKi 64
pKi 4.5 [64]
flavanone Rn Antagonist 4.5 pKi 64
pKi 4.5 [64]
MRS1066 Rn Antagonist 4.4 pKi 64
pKi 4.4 [64]
MRS1084 Rn Antagonist 4.4 pKi 64
pKi 4.4 [64]
MRS1191 Rn Antagonist 4.4 pKi 77
pKi 4.4 (Ki 4.01x10-5 M) [77]
caffeine Rn Antagonist 4.4 – 4.4 pKi 18,44
pKi 4.4 – 4.4 (Ki 4.4x10-5 – 4.1x10-5 M) [18,44]
MRS1062 Rn Antagonist 4.3 pKi 64
pKi 4.3 [64]
View species-specific antagonist tables
Antagonist Comments
Reference [22] does not use a transfected cell system but measures binding to the human hippocampus.

Istradefylline pKi values 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 Affinity Units Reference
VPC171 Hs Positive - - 5,51
[5,51]
Allosteric Modulator Comments
In vitro, VPC171 enhances A1R agonist ((R)-PIA)-induced ERK1/2 phosphorylation with a 2.4-fold positive cooperativity, and enhances [35S]GTPγS binding with a 6.9-fold positive cooperativity under the same conditions [51].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  15,56
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gq/G11 family
Adenylate cyclase stimulation
Phospholipase C stimulation
References:  15
Tissue Distribution
Brain > heart, kidney, lung.
Species:  Human
Technique:  Northern blotting.
References:  113
Spermatozoa.
Species:  Human
Technique:  immunocytochemistry.
References:  90
Adopicytes.
Species:  Human
Technique:  Northern blotting.
References:  12
Jejunum, ileum, colon.
Species:  Human
Technique:  RT-PCR.
References:  14
Brain (cerebral cortex, hippocampus), spinal cord and trigeminal ganglia.
Species:  Human
Technique:  Immunohistochemistry.
References:  117
Kidney: medullary tubular structures.
Species:  Mouse
Technique:  RNAse protection and RT-PCR.
References:  136
Jejunum.
Species:  Mouse
Technique:  RT-PCR.
References:  38
Brain: cerebral cortex.
Species:  Mouse
Technique:  Autoradiography.
References:  79
Brain: cortex, cerebellum, hippocampus > olfactory bulb, mesencephalon, striatum.
Species:  Rat
Technique:  Northern blotting.
References:  85
Kidney: medullary tubular structures.
Species:  Rat
Technique:  RNAse protection and RT-PCR.
References:  136
CNS: spinal cord lumbar dorsal horn.
Species:  Rat
Technique:  Immunohistochemistry.
References:  122
Testes: Sertoli cells >> spermatogonia, spermatocytes.
Species:  Rat
Technique:  in situ hybridisation.
References:  109
Spermatozoa.
Species:  Rat
Technique:  immunocytochemistry.
References:  90
Spleen, stomach, heart, testis.
Species:  Rat
Technique:  Northern blotting.
References:  85
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 CHO cells transfected with the mouse A1 receptor.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  139
Measurement of cAMP levels in CHO.K1 cells transfected with the human A1 receptor.
Species:  Human
Tissue:  CHO.K1 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  130
Measurement of cAMP levels in CHO cells transfected with the rat A1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  85
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:  121
Measurement of PKB activity in cardiomyocytes endogenously expressing the A1 receptor.
Species:  Rat
Tissue:  Cardiomyocytes.
Response measured:  PKB phosphorylation via Gi/o.
References:  37
Physiological Functions
Inhibition of renin release.
Species:  Rat
Tissue:  In vivo.
References:  93,104
Hypothermia and sedation.
Species:  Mouse
Tissue:  In vivo.
References:  3
Analgesia.
Species:  Rat
Tissue:  In vivo.
References:  34,124,141
Antinociception.
Species:  Rat
Tissue:  In vivo.
References:  63,82,106
Neuronal excitation of the superficial grey layer of the superior colliculus.
Species:  Rat
Tissue:  In vivo (superior colliculus).
References:  47
Antinociception.
Species:  Human
Tissue:  In vivo.
References:  39
Antinociception.
Species:  Mouse
Tissue:  In vivo.
References:  140
Macula densa control of renal vascular tone.
Species:  Mouse
Tissue:  In vivo (kidney).
References:  127
Mediation of tubuloglomerular feedback (TGF).
Species:  Rat
Tissue:  In vivo (kidney).
References:  118,128
Mediation of tubuloglomerular feedback (TGF).
Species:  Mouse
Tissue:  In vivo (kidney).
References:  11
Role in spermatozoa capacitation.
Species:  Human
Tissue:  Sperm.
References:  2
Presynaptic modulation of ACh release from the neuromuscular junction.
Species:  Mouse
Tissue:  Diaphragm muscle.
References:  21
Regulation of leptin production.
Species:  Rat
Tissue:  In vivo.
References:  108
Induction of chloride secretion.
Species:  Mouse
Tissue:  Jejunum.
References:  38
Inhibition of renin release.
Species:  Mouse
Tissue:  Kidney.
References:  123
Hypotension and bradycardia.
Species:  Rat
Tissue:  In vivo.
References:  9
Preconditioning.
Species:  Rat
Tissue:  Cardiomyocytes.
References:  36-37
Modulation of myenteric reflex.
Species:  Rat
Tissue:  Ileum.
References:  126
Chemotaxis.
Species:  Human
Tissue:  Immature plasmacytoid dendritic cells.
References:  119
Ca2+-mediated glycogenolysis.
Species:  Rat
Tissue:  Hepatocytes.
References:  43
Edema and leukocyte infiltration.
Species:  Rat
Tissue:  In vivo (pancreas).
References:  114
Regulation of glutamate release.
Species:  Rat
Tissue:  Cerebellar neurones.
References:  23
Regulation of glutamate release.
Species:  Rat
Tissue:  Hippocampal pyramidal neurons.
References:  120
Anticonvulsant activity.
Species:  Rat
Tissue:  Neocortex slices.
References:  98
Regulation of glutamate release and cell excitability.
Species:  Rat
Tissue:  Hippocampal slices.
References:  25
Neuroprotection.
Species:  Rat
Tissue:  Hippocampus.
References:  83
Arteriolar constriction.
Species:  Rat
Tissue:  Kidney.
References:  93
Physiological Consequences of Altering Gene Expression
A1 KO mice show hyperalgesia
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  57,