A<sub>1</sub> receptor | Adenosine receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

A₁ receptor

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 18

Nomenclature: A₁ receptor

Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Natural/Endogenous Ligands
Agonists
Antagonists
Allosteric Modulators
Immunopharmacology Comments
Immuno Cell Type Associations
Immuno Process Associations
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
General Comments
References
Contributors
How to cite this page

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	86,117,141
Mouse	7	326	1 E4	Adora1	adenosine A1 receptor	95,152
Rat	7	326	13q13	Adora1	adenosine A1 receptor	94

Previous and Unofficial Names
RDC7 \| adenosine receptor A1 \| A1-AR \| A1R

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
Alphafold	P30542 (Hs), Q60612 (Mm), P25099 (Rn)
ChEMBL Target	CHEMBL226 (Hs), CHEMBL3688 (Mm), CHEMBL318 (Rn)
DrugBank Target	P30542 (Hs)
Ensembl Gene	ENSG00000163485 (Hs), ENSMUSG00000042429 (Mm), ENSRNOG00000003442 (Rn)
Entrez Gene	134 (Hs), 11539 (Mm), 29290 (Rn)
Human Protein Atlas	ENSG00000163485 (Hs)
KEGG Gene	hsa:134 (Hs), mmu:11539 (Mm), rno:29290 (Rn)
OMIM	102775 (Hs)
Pharos	P30542 (Hs)
RefSeq Nucleotide	NM_000674 (Hs), NM_001008533 (Mm), NM_017155 (Rn)
RefSeq Protein	NP_000665 (Hs), NP_001008533 (Mm), NP_058851 (Rn)
UniProtKB	P30542 (Hs), Q60612 (Mm), P25099 (Rn)
Wikipedia	ADORA1 (Hs)

Selected 3D Structures

Image of receptor 3D structure from RCSB PDB

Description:	Crystal structure of the human adenosine A1 receptor A1AR-bRIL in complex with the covalent antagonist DU172 at 3.2A resolution
PDB Id:	5UEN
Ligand:	DU172
Resolution:	3.2Å
Species:	Human
References:	49

Description:	Crystal structure of stabilized A1 receptor in complex with PSB36
PDB Id:	5N2S
Ligand:	PSB36
Resolution:	3.3Å
Species:	Human
References:	18

Description:	Structure of the adenosine-bound human adenosine A₁ receptor–G_i complex
PDB Id:	6D9H
Ligand:	adenosine
Resolution:	3.6Å
Species:	Human
References:	30

Natural/Endogenous Ligands
adenosine

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Agonists

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]CCPA		Hs	Full agonist	9.2	pK_d	78,120
⤷	pK_d 9.2 (K_d 6.31x10^-10 M) [78,120]
5-Cl-5-deoxy-(±)-ENBA		Hs	Full agonist	9.3	pK_i	36
⤷	pK_i 9.3 (K_i 5.1x10^-10 M) [36]
N(6)-cyclohexyladenosine		Rn	Agonist	9.1	pK_i	24
⤷	pK_i 9.1 (K_i 8.5x10^-10 M) [24]
(R)-PIA		Rn	Agonist	8.9	pK_i	24
⤷	pK_i 8.9 (K_i 1.2x10^-9 M) [24]
CCPA		Rn	Agonist	8.9	pK_i	85
⤷	pK_i 8.9 (K_i 1.3x10^-9 M) [85]
(R,S)-PHPNECA		Hs	Full agonist	8.6	pK_i	148
⤷	pK_i 8.6 [148]
TCPA		Hs	Agonist	8.6	pK_i	9
⤷	pK_i 8.6 (K_i 2.8x10^-9 M) [9]
GR79236		Rn	Agonist	8.5	pK_i	63
⤷	pK_i 8.5 (K_i 3.1x10^-9 M) [63]
NECA		Rn	Agonist	8.3	pK_i	90
⤷	pK_i 8.3 (K_i 5.1x10^-9 M) [90]
tecadenoson		Pig	Agonist	8.2	pK_i	63,105
⤷	pK_i 8.2 (K_i 6.5x10^-9 M) [63,105]
2-chloroadenosine		Rn	Agonist	8.2	pK_i	24
⤷	pK_i 8.2 (K_i 6.7x10^-9 M) [24]
compound 10 [PMID: 31306001]		Hs	Inverse agonist	8.1	pK_i	8
⤷	pK_i 8.1 (K_i 7.22x10^-9 M) [8] Description: Binding affinity calculated by measuring displacement of specific [³H]DPCPX binding at hA₁ARs expressed in CHO cells.
cyclopentyladenosine		Hs	Full agonist	6.5 – 9.4	pK_i	22,25,41,54,63-64,120
⤷	pK_i 6.5 – 9.4 [22,25,41,54,63-64,120]
CCPA		Hs	Full agonist	7.7 – 8.1	pK_i	63,110
⤷	pK_i 7.7 – 8.1 [63,110]
MRS3558		Mm	Agonist	7.8	pK_i	85
⤷	pK_i 7.8 (K_i 1.58x10^-8 M) [85]
LUF5831		Hs	Partial agonist	7.7	pK_i	54
⤷	pK_i 7.7 [54]
(R)-PIA		Hs	Full agonist	6.4 – 8.7	pK_i	41,64,78,120,140
⤷	pK_i 6.4 – 8.7 [41,64,78,120,140]
Cl-IB-MECA		Mm	Agonist	7.5	pK_i	85
⤷	pK_i 7.5 (K_i 3.5x10^-8 M) [85]
piclidenoson		Hs	Agonist	7.3	pK_i	63
⤷	pK_i 7.3 (K_i 5.1x10^-8 M) [63]
GS9667		Hs	Agonist	7.3	pK_i	34
⤷	pK_i 7.3 (K_i 5.5x10^-8 M) [34]
2-hexynyl-NECA		Hs	Full agonist	7.2	pK_i	148
⤷	pK_i 7.2 [148]
adenosine		Rn	Agonist	7.1	pK_i	155
⤷	pK_i 7.1 (K_i 7.3x10^-8 M) [155]
apadenoson		Hs	Agonist	7.1	pK_i	63
⤷	pK_i 7.1 (K_i 7.7x10^-8 M) [63]
adenosine		Hs	Agonist	~7.0	pK_i	155
⤷	pK_i ~7.0 (K_i ~1x10^-7 M) [155]
MRS3558		Rn	Agonist	7.0	pK_i	85
⤷	pK_i 7.0 (K_i 1.05x10^-7 M) [85]
NECA		Hs	Full agonist	5.3 – 8.2	pK_i	41,64,120,140,155
⤷	pK_i 5.3 – 8.2 [41,64,120,140,155]
Cl-IB-MECA		Hs	Agonist	6.7	pK_i	63
⤷	pK_i 6.7 (K_i 2.2x10^-7 M) [63]
MRS3558		Hs	Agonist	6.6	pK_i	63
⤷	pK_i 6.6 (K_i 2.6x10^-7 M) [63]
Cl-IB-MECA		Rn	Agonist	6.6	pK_i	85
⤷	pK_i 6.6 (K_i 2.8x10^-7 M) [85]
HEMADO		Hs	Agonist	6.5	pK_i	77,148
⤷	pK_i 6.5 (K_i 3.3x10^-7 M) [77,148]
PENECA		Hs	Full agonist	6.2	pK_i	148
⤷	pK_i 6.2 [148]
CGS 21680		Hs	Full agonist	5.8 – 6.4	pK_i	41,63
⤷	pK_i 5.8 – 6.4 [41,63]
CGS 21680		Rn	Agonist	5.7	pK_i	85
⤷	pK_i 5.7 (K_i 1.8x10^-6 M) [85]
2-chloroadenosine		Hs	Full agonist	5.2 – 5.6	pK_i	64,120
⤷	pK_i 5.2 – 5.6 [64,120]
(S)-PIA		Hs	Full agonist	4.6 – 6.0	pK_i	64,140
⤷	pK_i 4.6 – 6.0 [64,140]
CP608,039		Hs	Agonist	5.1	pK_i	63
⤷	pK_i 5.1 (K_i 7.3x10^-6 M) [63]
BAY 60-6583		Hs	Agonist	<5.0	pK_i	81
⤷	pK_i <5.0 (K_i >1x10^-5 M) [81]
regadenoson		Hs	Agonist	<5.0	pK_i	63
⤷	pK_i <5.0 (K_i >1x10^-5 M) [63]
MRS5151		Mm	Agonist	5.0	pK_i	99
⤷	pK_i 5.0 (K_i 1.05x10^-5 M) [99]
MRS5151		Hs	Agonist	4.8	pK_i	99
⤷	pK_i 4.8 (K_i 1.49x10^-5 M) [99]
binodenoson		Hs	Agonist	4.3	pK_i	63
⤷	pK_i 4.3 (K_i 4.8x10^-5 M) [63]
capadenoson		Hs	Partial agonist	10.0	pEC₅₀	2
⤷	pEC₅₀ 10.0 (EC₅₀ 1x10^-10 M) [2]
neladenoson		Hs	Partial agonist	10.0	pEC₅₀	98
⤷	pEC₅₀ 10.0 (EC₅₀ 1x10^-10 M) [98]
MRS7469		Hs	Agonist	-	-	139
⤷	[139]

View species-specific agonist tables

Agonist Comments

The role for adenosine as endogenous ligand for the A1 receptor is described in [37] and [38].

The role for adenosine as endogenous ligand for the A₁ receptor is described in [38] and [39].

Capadenoson and neladenoson have been evaluated in phase 2 clinical trials for heart failure, but failed to meet expectations [149].

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

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]DPCPX		Hs	Antagonist	8.4 – 9.2	pK_d	22,35,78,112,120,140
⤷	pK_d 8.4 – 9.2 (K_d 1.2x10^-9 – 6x10^-10 M) [22,35,78,112,120,140]
xanthine amine congener		Hs	Antagonist	7.5	pK_d	36
⤷	pK_d 7.5 [36]
PSB36		Rn	Antagonist	9.9	pK_i	1
⤷	pK_i 9.9 (K_i 1.24x10^-10 M) [1]
DPCPX		Rn	Antagonist	9.0 – 9.7	pK_i	74,79,151
⤷	pK_i 9.0 – 9.7 (K_i 1x10^-9 – 1.8x10^-10 M) [74,79,151]
CPFPX		Rn	Antagonist	9.2	pK_i	57
⤷	pK_i 9.2 (K_i 6.3x10^-10 M) [57]
LUF5981		Hs	Antagonist	9.1	pK_i	17
⤷	pK_i 9.1 (K_i 9x10^-10 M) [17]
derenofylline		Hs	Antagonist	9.0	pK_i	68
⤷	pK_i 9.0 (K_i 1x10^-9 M) [68]
FR194921		Hs	Antagonist	8.9	pK_i	93
⤷	pK_i 8.9 [93]
CPFPX		Hs	Antagonist	8.9	pK_i	57
⤷	pK_i 8.9 (K_i 1.26x10^-9 M) [57]
tonapofylline		Rn	Antagonist	8.9	pK_i	73
⤷	pK_i 8.9 (K_i 1.3x10^-9 M) [73]
rolofylline		Rn	Antagonist	7.9 – 9.7	pK_i	115
⤷	pK_i 7.9 – 9.7 (K_i 1.26x10^-8 – 1.9x10^-10 M) [115]
WRC-0571		Hs	Antagonist	8.8	pK_i	96
⤷	pK_i 8.8 [96]
rolofylline		Hs	Antagonist	8.1 – 9.1	pK_i	73,115
⤷	pK_i 8.1 – 9.1 (K_i 8x10^-9 – 7.2x10^-10 M) [73,115]
derenofylline		Rn	Antagonist	8.6	pK_i	68
⤷	pK_i 8.6 (K_i 2.51x10^-9 M) [68]
CGS 15943		Hs	Antagonist	8.5	pK_i	112
⤷	pK_i 8.5 (K_i 3.5x10^-9 M) [112]
DPCPX		Hs	Antagonist	7.4 – 9.2	pK_i	25,60,110,120,151
⤷	pK_i 7.4 – 9.2 (K_i 3.98x10^-8 – 6.3x10^-10 M) [25,60,110,120,151]
CGS 15943		Rn	Antagonist	8.2	pK_i	89
⤷	pK_i 8.2 (K_i 6.4x10^-9 M) [89]
tonapofylline		Hs	Antagonist	8.1	pK_i	73
⤷	pK_i 8.1 (K_i 7.4x10^-9 M) [73]
MRS1754		Rn	Antagonist	7.8	pK_i	75
⤷	pK_i 7.8 (K_i 1.68x10^-8 M) [75]
8-cyclopentyltheophylline		Hs	Antagonist	7.5 – 8.0	pK_i	22
⤷	pK_i 7.5 – 8.0 [22]
FK-453		Hs	Antagonist	7.7	pK_i	63
⤷	pK_i 7.7 (K_i 1.8x10^-8 M) [63]
xanthine amine congener		Hs	Antagonist	7.6	pK_i	64
⤷	pK_i 7.6 [64]
DU172		Hs	Antagonist	7.4	pK_i	49
⤷	pK_i 7.4 [49]
vipadenant		Hs	Antagonist	7.2	pK_i	46
⤷	pK_i 7.2 (K_i 6.8x10^-8 M) [46]
ST-1535		Hs	Antagonist	7.1	pK_i	102
⤷	pK_i 7.1 (K_i 7.18x10^-8 M) [102]
imaradenant		Hs	Antagonist	6.8	pK_i	12
⤷	pK_i 6.8 (K_i 1.6x10^-7 M) [12] Description: Binding affinity of AZD4635 determined in a radioligand binding competition assays with membranes prepared from CHO cells stably expressing human A1R.
MRE 2029F20		Hs	Antagonist	6.7	pK_i	7,144
⤷	pK_i 6.7 [7,144]
istradefylline		Rn	Antagonist	6.6	pK_i	39
⤷	pK_i 6.6 (K_i 2.3x10^-7 M) [39]
AS70		Hs	Antagonist	6.6	pK_i	144
⤷	pK_i 6.6 [144]
AS100		Hs	Antagonist	6.5	pK_i	144
⤷	pK_i 6.5 [144]
ATL802		Hs	Antagonist	6.4	pK_i	75
⤷	pK_i 6.4 (K_i 3.69x10^-7 M) [75]
MRS1754		Hs	Antagonist	6.4	pK_i	75
⤷	pK_i 6.4 (K_i 4.03x10^-7 M) [75]
PSB-11		Rn	Antagonist	6.4	pK_i	113
⤷	pK_i 6.4 (K_i 4.4x10^-7 M) [113]
ZM-241385		Hs	Antagonist	6.1 – 6.6	pK_i	63,112
⤷	pK_i 6.1 – 6.6 [63,112]
MRS928		Rn	Antagonist	6.3	pK_i	72
⤷	pK_i 6.3 [72]
L-97-1		Hs	Antagonist	6.2	pK_i	110
⤷	pK_i 6.2 [110]
MRS1041		Rn	Antagonist	6.2	pK_i	72
⤷	pK_i 6.2 [72]
SCH 58261		Hs	Antagonist	6.1 – 6.3	pK_i	63,112,140
⤷	pK_i 6.1 – 6.3 [63,112,140]
mefloquine		Hs	Antagonist	6.2	pK_i	150
⤷	pK_i 6.2 (K_i 6.75x10^-7 M) [150] Description: Binding affinity determined by displacement of [³H]-DPCPX from human A₁ receptors by increasing concentrations of racemic mefloquine.
AS99		Hs	Antagonist	6.1	pK_i	144
⤷	pK_i 6.1 [144]
galangin		Rn	Antagonist	6.1	pK_i	72
⤷	pK_i 6.1 [72]
LUF7602		Hs	Antagonist	6.1	pK_i	157
⤷	pK_i 6.1 (K_i 7.94x10^-7 M) [157] Description: Affinity determined from the displacement of specific [³H]DPCPX binding on CHO cell membranes stably expressing human adenosine A₁ receptors at 25 °C during 2 h of incubation.
PSB-10		Rn	Antagonist	6.1	pK_i	107
⤷	pK_i 6.1 (K_i 8.05x10^-7 M) [107]
istradefylline		Hs	Antagonist	6.1	pK_i	39
⤷	pK_i 6.1 (K_i 8.41x10^-7 M) [39]
MSX-2		Rn	Antagonist	6.1	pK_i	125
⤷	pK_i 6.1 (K_i 9x10^-7 M) [125]
MRS1042		Rn	Antagonist	6.0	pK_i	72
⤷	pK_i 6.0 [72]
preladenant		Hs	Antagonist	<6.0	pK_i	104
⤷	pK_i <6.0 (K_i >1x10^-6 M) [104]
MRE 3008F20		Hs	Antagonist	5.9 – 6.0	pK_i	63,144-145
⤷	pK_i 5.9 – 6.0 [63,144-145]
SCH442416		Hs	Antagonist	5.9	pK_i	63
⤷	pK_i 5.9 (K_i 1.11x10^-6 M) [63]
PSB-11		Hs	Antagonist	5.8	pK_i	113
⤷	pK_i 5.8 (K_i 1.64x10^-6 M) [113]
PSB-10		Hs	Antagonist	5.8	pK_i	113
⤷	pK_i 5.8 (K_i 1.7x10^-6 M) [113]
KF26777		Hs	Antagonist	5.7	pK_i	121
⤷	pK_i 5.7 (K_i 1.8x10^-6 M) [121]
CVT-6883		Hs	Antagonist	5.7	pK_i	33
⤷	pK_i 5.7 (K_i 1.94x10^-6 M) [33]
MRS1093		Rn	Antagonist	5.7	pK_i	72
⤷	pK_i 5.7 [72]
PSB1115		Rn	Antagonist	5.7	pK_i	106
⤷	pK_i 5.7 (K_i 2.2x10^-6 M) [106]
MRS1132		Rn	Antagonist	5.6	pK_i	72
⤷	pK_i 5.6 [72]
MSX-2		Hs	Antagonist	5.6	pK_i	125
⤷	pK_i 5.6 (K_i 2.5x10^-6 M) [125]
LAS38096		Hs	Antagonist	5.6	pK_i	32,146
⤷	pK_i 5.6 (K_i 2.821x10^-6 M) [32,146]
flavone		Rn	Antagonist	5.5	pK_i	72
⤷	pK_i 5.5 [72]
isobutylmethylxanthine		Hs	Antagonist	5.1	pK_i	64
⤷	pK_i 5.1 [64]
sakuranetin		Rn	Antagonist	5.1	pK_i	72
⤷	pK_i 5.1 [72]
theophylline		Hs	Antagonist	4.9 – 5.2	pK_i	35,64,78,144
⤷	pK_i 4.9 – 5.2 [35,64,78,144]
ATL802		Mm	Antagonist	5.0	pK_i	75
⤷	pK_i 5.0 (K_i 9.583x10^-6 M) [75]
MRS1191		Hs	Antagonist	<5.0	pK_i	85
⤷	pK_i <5.0 (K_i >1x10^-5 M) [85]
MRS1523		Hs	Antagonist	<5.0	pK_i	85
⤷	pK_i <5.0 (K_i >1x10^-5 M) [85]
VUF5574		Rn	Antagonist	>5.0	pK_i	143
⤷	pK_i >5.0 (K_i <1x10^-5 M) [143]
PSB603		Hs	Antagonist	<5.0	pK_i	13
⤷	pK_i <5.0 (K_i >1x10^-5 M) [13]
PSB603		Rn	Antagonist	<5.0	pK_i	13
⤷	pK_i <5.0 (K_i >1x10^-5 M) [13]
PSB1115		Hs	Antagonist	<5.0	pK_i	53
⤷	pK_i <5.0 (K_i >1x10^-5 M) [53]
theophylline		Rn	Antagonist	4.8 – 5.1	pK_i	61,106
⤷	pK_i 4.8 – 5.1 (K_i 1.4x10^-5 – 8.74x10^-6 M) [61,106]
morin		Rn	Antagonist	4.9	pK_i	72
⤷	pK_i 4.9 [72]
MRS1523		Rn	Antagonist	4.8	pK_i	85
⤷	pK_i 4.8 (K_i 1.56x10^-5 M) [85]
caffeine		Hs	Antagonist	4.3 – 5.0	pK_i	1,27,61
⤷	pK_i 4.3 – 5.0 (K_i 4.49x10^-5 – 1.07x10^-5 M) [1,27,61]
MRS923		Rn	Antagonist	4.6	pK_i	72
⤷	pK_i 4.6 [72]
CSC		Rn	Antagonist	4.6	pK_i	62
⤷	pK_i 4.6 (K_i 2.8x10^-5 M) [62]
MRS1065		Rn	Antagonist	4.5	pK_i	72
⤷	pK_i 4.5 [72]
MRS1086		Rn	Antagonist	4.5	pK_i	72
⤷	pK_i 4.5 [72]
flavanone		Rn	Antagonist	4.5	pK_i	72
⤷	pK_i 4.5 [72]
MRS1066		Rn	Antagonist	4.4	pK_i	72
⤷	pK_i 4.4 [72]
MRS1084		Rn	Antagonist	4.4	pK_i	72
⤷	pK_i 4.4 [72]
MRS1191		Rn	Antagonist	4.4	pK_i	85
⤷	pK_i 4.4 (K_i 4.01x10^-5 M) [85]
caffeine		Rn	Antagonist	4.4 – 4.4	pK_i	23,51
⤷	pK_i 4.4 – 4.4 (K_i 4.4x10^-5 – 4.1x10^-5 M) [23,51]
MRS1062		Rn	Antagonist	4.3	pK_i	72
⤷	pK_i 4.3 [72]
LUF5962		Hs	Antagonist	7.1	pIC₅₀	52
⤷	pIC₅₀ 7.1 [52]

View species-specific antagonist tables

Antagonist Comments

Reference [27] 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

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Ligand		Sp.	Action	Value	Parameter	Reference
VPC171		Hs	Positive	-	-	6,59
⤷	[6,59]
PD81723		Hs	Positive	-	-	15
⤷	[15]

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 [59].

Immunopharmacology Comments
Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A₁ receptor in adenosine-mediated anti-inflammatory effects is not fully understood.

Immunopharmacology Comments

Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A₁ receptor in adenosine-mediated anti-inflammatory effects is not fully understood.

Cell Type Associations

Immuno Cell Type:	T cells
Cell Ontology Term:	type I NK T cell (CL:0000921)
Comment:	A₁ receptor is expressed by mouse iNKT cells.
References:	108

Immuno Process Associations

Immuno Process:

Inflammation

Immuno Process:

Immune regulation

Immuno Process:

Chemotaxis & migration

Primary Transduction Mechanisms
Transducer	Effector/Response
G_i/G_o family	Adenylyl cyclase inhibition
References: 20,64

Secondary Transduction Mechanisms
Transducer	Effector/Response
G_s family G_q/G₁₁ family	Adenylyl cyclase stimulation Phospholipase C stimulation
References: 20

Tissue Distribution

Brain > heart, kidney, lung.

Species:	Human
Technique:	Northern blotting.
References:	123

Spermatozoa.

Species:	Human
Technique:	immunocytochemistry.
References:	100

Adopicytes.

Species:	Human
Technique:	Northern blotting.
References:	16

Jejunum, ileum, colon.

Species:	Human
Technique:	RT-PCR.
References:	19

Brain (cerebral cortex, hippocampus), spinal cord and trigeminal ganglia.

Species:	Human
Technique:	Immunohistochemistry.
References:	127

Kidney: medullary tubular structures.

Species:	Mouse
Technique:	RNAse protection and RT-PCR.
References:	147

Jejunum.

Species:	Mouse
Technique:	RT-PCR.
References:	44

Brain: cerebral cortex.

Species:	Mouse
Technique:	Autoradiography.
References:	88

Brain: cortex, cerebellum, hippocampus > olfactory bulb, mesencephalon, striatum.

Species:	Rat
Technique:	Northern blotting.
References:	94

Kidney: medullary tubular structures.

Species:	Rat
Technique:	RNAse protection and RT-PCR.
References:	147

CNS: spinal cord lumbar dorsal horn.

Species:	Rat
Technique:	Immunohistochemistry.
References:	132

Testes: Sertoli cells >> spermatogonia, spermatocytes.

Species:	Rat
Technique:	in situ hybridisation.
References:	119

Spermatozoa.

Species:	Rat
Technique:	immunocytochemistry.
References:	100

Spleen, stomach, heart, testis.

Species:	Rat
Technique:	Northern blotting.
References:	94

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:	152

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:	141

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:	94

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:	131

Measurement of PKB activity in cardiomyocytes endogenously expressing the A₁ receptor.

Species:	Rat
Tissue:	Cardiomyocytes.
Response measured:	PKB phosphorylation via G_i/o.
References:	43

Physiological Functions

Antinociception.

Species:	Rat
Tissue:	In vivo.
References:	71,91,116

Inhibition of renin release.

Species:	Rat
Tissue:	In vivo.
References:	103,114

Hypothermia and sedation.

Species:	Mouse
Tissue:	In vivo.
References:	4

Analgesia.

Species:	Rat
Tissue:	In vivo.
References:	40,134,154

Neuronal excitation of the superficial grey layer of the superior colliculus.

Species:	Rat
Tissue:	In vivo (superior colliculus).
References:	55

Antinociception.

Species:	Human
Tissue:	In vivo.
References:	45

Antinociception.

Species:	Mouse
Tissue:	In vivo.
References:	153

Macula densa control of renal vascular tone.

Species:	Mouse
Tissue:	In vivo (kidney).
References:	137

Mediation of tubuloglomerular feedback (TGF).

Species:	Rat
Tissue:	In vivo (kidney).
References:	128,138

Mediation of tubuloglomerular feedback (TGF).

Species:	Mouse
Tissue:	In vivo (kidney).
References:	14

Role in spermatozoa capacitation.

Species:	Human
Tissue:	Sperm.
References:	3

Presynaptic modulation of ACh release from the neuromuscular junction.

Species:	Mouse
Tissue:	Diaphragm muscle.
References:	26

Regulation of leptin production.

Species:	Rat
Tissue:	In vivo.
References:	118

Induction of chloride secretion.

Species:	Mouse
Tissue:	Jejunum.
References:	44

Inhibition of renin release.

Species:	Mouse
Tissue:	Kidney.
References:	133

Hypotension and bradycardia.

Species:	Rat
Tissue:	In vivo.
References:	11

Preconditioning.

Species:	Rat
Tissue:	Cardiomyocytes.
References:	42-43

Modulation of myenteric reflex.

Species:	Rat
Tissue:	Ileum.
References:	136

Chemotaxis.

Species:	Human
Tissue:	Immature plasmacytoid dendritic cells.
References:	129

Ca²⁺-mediated glycogenolysis.

Species:	Rat
Tissue:	Hepatocytes.
References:	50

Edema and leukocyte infiltration.

Species:	Rat
Tissue:	In vivo (pancreas).
References:	124

Regulation of glutamate release.

Species:	Rat
Tissue:	Cerebellar neurones.
References:	28

Regulation of glutamate release.

Species:	Rat
Tissue:	Hippocampal pyramidal neurons.
References:	130

Anticonvulsant activity.

Species:	Rat
Tissue:	Neocortex slices.
References:	109

Regulation of glutamate release and cell excitability.

Species:	Rat
Tissue:	Hippocampal slices.
References:	31

Neuroprotection.

Species:	Rat
Tissue:	Hippocampus.
References:	92

Arteriolar constriction.

Species:	Rat
Tissue:	Kidney.
References:	103

Physiological Consequences of Altering Gene Expression

Transgenic mice overexpressing adipocyte A₁ receptors exhibit protection from developing insulin-resistance.

Species:	Mouse
Tissue:
Technique:	Transgenesis.
References:	29

A₁ receptor knockout mice exhibit increased anxiety when compared to the wild-type. Thermal hyperalgaesia is also observed and the antinociceptive effect of adenosine receptor agonists is abolished.
In vitro hippocampal slices from the knockout mice have altered excitatory glutamatergic neurotransmission in response to adenosine, theophylline and hypoxia.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	65

A₁ receptor knockout mice lack the normal tubuloglomerular feedback exhibited by wild-type mice.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	14,137

A₁ receptor knockout mice exhibit reduced activity and exploratory behaviour and increased anxiety and aggressiveness.

Species:	Mouse
Tissue:
Technique:
References:	47

A₁ receptor knockout mice exhibit emotional instability.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	82

A₁ receptor knockout mice have reduced fertility when compared to wild-type mice due to reduced spermatozoa capacitation.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	101

Transgenic mice overexpressing the A₁ receptor exhibit additional cardioprotection during ischemia.

Species:	Mouse
Tissue:
Technique:	Transgenesis.
References:	21,97

A₁ receptor knockout mice exhibit reduced hypoxia-induced ventriculomegaly (enlargement of the ventricles in the brain) and loss of white matter.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	142

The effect of adenosine on chloride secretion is abolished in the jejunum of A₁ receptor knockout mice.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	44

A₁ receptor knockout mice exhibit heat hypersensitivity and hyperalgesia when compared to the wild-type.
In addition, the antinociceptive effect of intrathecally administered morphine was reduced.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	153

A₁ receptor knockout mice exhibit reduced habituation to an environment.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	48

Wlid-type and A₁ receptor knockout mice were subjected to renal ischemia and reperfusion. The mice lacking the A₁ receptor exhibited greater renal injury.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	84

Transgenic mice overexpressing the A₁ receptor exhibit sinus and atrioventricular node dysfunction and supraventricular arrhythmias.

Species:	Mouse
Tissue:
Technique:	Transgenesis.
References:	76

A₁ receptor knockout mice develop status epilepticus following controlled cortical impact.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	80

A₁ receptor knockout mice exhibit no increase in brain damage following ischemia. However, wild-type mice do show increased damage with DPCPX application, implying that some compensatory mechanism may be recruited in the knockout mice.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	111

Focal deletion of the A₁ receptor from specific hippocampal regions results in impaired recovery of synaptic transmission following hypoxia.

Species:	Mouse
Tissue:
Technique:	Focal viral-mediated elimination.
References:	5

Focal deletion of the A1 receptor from CA3 hippocampal neurons results in elimination of the postsynaptic response to adenosine. Deletion from the CA1 region has no effect, showing that adenosine inhibits signalling between CA3 and CA1 in a presynaptic manner.

Species:	Mouse
Tissue:
Technique:	Focal viral-mediated elimination.
References:	126

In A1 receptor KO mice pulses of insulin release are unmasked and those of glucagon and somatostatin prolonged.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	122

In A1 receptor KO mice an increase in fat mass and higher levels of free fatty acids, glycerol and triglycerides are observed.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	66

Adenosine modulation of CB1 receptor function is absent in A1 receptor KO mice

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells
References:	56

Fat cells prepared from A1 KO mice show increased lipolysis, both basal and stimulated.

Species:	Mouse
Tissue:	Adipose tissue, fat cells
Technique:	Gene targeting in embryonic stem cells.
References:	67

Conditional CNS knockout of the A1 receptor causes attenuation of the slow-wave activity rebound response to restricted sleep, but not sleep duration. But global A1 KO does not alter sleep-wakefulness.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	10,58,135

A1 receptor KO mice had a slightly elevated heart rate compared to WT, particularly in males. Body temperature was higher in A1 receptor KO males and females; locomotor activity was higher in A1 receptor KO females, but not in males.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	156

A1 receptor KO mice show increased renal blood flow, absence of tubuloglomerular feedback and increased renin secretion.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	14,137

A1 KO mice show decreased osteoclast activity and increased bone mass.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	69-70

A1 KO mice show altered respiratory drive.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells
References:	65

A1 KO mice show hyperalgesia

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells
References:	65,153

A1 KO mice show reduced sperm motility and fertility

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells
References:	101

A1 receptor KO mice show reduced capacity for preconditioning.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	83

A₁ receptor knockout mice exhibit an increased blood pressure and plasma renin activity when compared to wild-type mice.

Species:	Mouse
Tissue:
Technique:	Gene targeting in embryonic stem cells.
References:	14

A₁ receptor deletion inhibits tumour development in vivo in immune-deficient xenografts.

Species:	Mouse
Tissue:	Human melanoma cell lines.
Technique:	CRISPR editing.
References:	87

Phenotypes, Alleles and Disease Models

Mouse data from MGI

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Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0001777	abnormal body temperature regulation	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0002206	abnormal CNS synaptic transmission	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0002910	abnormal excitatory postsynaptic currents	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0002912	abnormal excitatory postsynaptic potential	PMID: 11470917
Adora1^tm1Rgrn	Adora1^tm1Rgrn/Adora1^tm1Rgrn involves: 129S4/SvJae * C57BL/6	MGI:99401	MP:0002912	abnormal excitatory postsynaptic potential	PMID: 12843280
Adora1^tm1Rgrn	Adora1^tm1Rgrn/Adora1^tm1Rgrn involves: 129S4/SvJae * C57BL/6	MGI:99401	MP:0002272	abnormal nervous system electrophysiology	PMID: 12843280
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0002314	abnormal respiratory mechanics	PMID: 11470917
Adora1^tm1Jgsc	Adora1^tm1Jgsc/Adora1^tm1Jgsc involves: 129S1/Sv * 129X1/SvJ	MGI:99401	MP:0003638	abnormal response/metabolism to endogenous compounds	PMID: 15343381
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0002917	decreased synaptic depression	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0003998	decreased thermal nociceptive threshold	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0005407	hyperalgesia	PMID: 11470917
Adora1^tm1Bbf	Adora1^tm1Bbf/Adora1^tm1Bbf involves: 129P2/OlaHsd * C57BL	MGI:99401	MP:0001363	increased anxiety-related response	PMID: 11470917
Adora1^tm1Jgsc	Adora1^tm1Jgsc/Adora1^tm1Jgsc involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:99401	MP:0005553	increased circulating creatinine level	PMID: 17928414
Adora1^tm1Jgsc	Adora1^tm1Jgsc/Adora1^tm1Jgsc involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:99401	MP:0004041	increased susceptibility to kidney reperfusion injury	PMID: 17928414
Adora1^tm1Rgrn	Adora1^tm1Rgrn/Adora1^tm1Rgrn involves: 129S4/SvJae * C57BL/6	MGI:99401	MP:0002169	no abnormal phenotype detected	PMID: 12843280

General Comments
For a review of the effects of adenosine receptor knockout on nervous system function see reference [38].

References

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