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β1-adrenoceptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 28

Nomenclature: β1-adrenoceptor

Family: Adrenoceptors

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 7 477 10q25.3 ADRB1 adrenoceptor beta 1 29
Mouse 7 466 19 51.96 cM Adrb1 adrenergic receptor, beta 1 36
Rat 7 466 1q55 Adrb1 adrenoceptor beta 1 52
Previous and Unofficial Names Click here for help
ADRB1R | Adrenergic receptor beta 1 | B1AR | beta-1 adrenergic receptor | beta-1 adrenoreceptor | Adrb-1 | beta 1-AR | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb adrb1_human (Hs), adrb1_mouse (Mm), adrb1_rat (Rn)
Other databases
Alphafold P08588 (Hs), P34971 (Mm), P18090 (Rn)
ChEMBL Target CHEMBL213 (Hs), CHEMBL3440 (Mm), CHEMBL3252 (Rn)
DrugBank Target P08588 (Hs)
Ensembl Gene ENSG00000043591 (Hs), ENSMUSG00000035283 (Mm), ENSRNOG00000017002 (Rn)
Entrez Gene 153 (Hs), 11554 (Mm), 24925 (Rn)
Human Protein Atlas ENSG00000043591 (Hs)
KEGG Gene hsa:153 (Hs), mmu:11554 (Mm), rno:24925 (Rn)
OMIM 109630 (Hs)
Pharos P08588 (Hs)
RefSeq Nucleotide NM_000684 (Hs), NM_007419 (Mm), NM_012701 (Rn)
RefSeq Protein NP_000675 (Hs), NP_031445 (Mm), NP_036833 (Rn)
UniProtKB P08588 (Hs), P34971 (Mm), P18090 (Rn)
Wikipedia ADRB1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the β1-Adrenergic G Protein-Coupled Receptor
PDB Id:  2VT4
Ligand:  cyanopindolol
Resolution:  2.7Å
Species:  Turkey
References:  87
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and partial bound agonist Dobutamine
PDB Id:  2Y01
Ligand:  dobutamine
Resolution:  2.6Å
Species:  Turkey
References:  86
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and bound agonist Isoprenaline
PDB Id:  2Y03
Ligand:  isoprenaline
Resolution:  2.85Å
Species:  Turkey
References:  86
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and partial bound agonist Salbutamol
PDB Id:  2Y04
Ligand:  salbutamol
Resolution:  3.05Å
Species:  Turkey
References:  86
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and bound agonist Carazolol
PDB Id:  2YCW
Ligand:  carazolol
Resolution:  3.0Å
Species:  Turkey
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-Adrenergic receptor with stabilising mutations and bound antagonist Cyanopindolol
PDB Id:  2YCX
Ligand:  cyanopindolol
Resolution:  3.25Å
Species:  Turkey
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and partial bound agonist Dobutamine
PDB Id:  2Y00
Ligand:  dobutamine
Resolution:  2.5Å
Species:  Turkey
References:  86
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and bound antagonist Cyanopindolol
PDB Id:  2YCY
Ligand:  cyanopindolol
Resolution:  3.15Å
Species:  Turkey
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  NMR and circular dichroism studies of synthetic peptides derived from the third intracellular loop of the beta-adrenoceptor
PDB Id:  1DEP
Resolution:  0.0Å
Species:  Turkey
References:  41
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and bound agonist Carmoterol
PDB Id:  2Y02
Ligand:  carmoterol
Resolution:  2.6Å
Species:  Turkey
References:  86
Image of receptor 3D structure from RCSB PDB
Description:  Turkey β1-adrenergic receptor with stabilising mutations and bound antagonist Iodocyanopindolol
PDB Id:  2YCZ
Ligand:  iodocyanopindolol
Resolution:  3.65Å
Species:  Turkey
References:  61
Image of receptor 3D structure from RCSB PDB
Description:  Ultra-thermostable beta1-adrenoceptor with cyanopindolol bound
PDB Id:  4BVN
Ligand:  cyanopindolol
Resolution:  2.1Å
Species:  Turkey
References:  56
Image of receptor 3D structure from RCSB PDB
Description:  Structural basis of the activation of heterotrimeric Gs-protein by isoproterenol-bound β1-adrenoceptor.
PDB Id:  7JJO
Ligand:  isoprenaline
Resolution:  2.6Å
Species:  Turkey
References:  78
Image of receptor 3D structure from RCSB PDB
Description:  Thermostabilised β1-adrenoceptor with rationally designed inverse agonist 7-methylcyanopindolol bound.
PDB Id:  5A8E
Ligand:  7-methylcyanopindolol
Resolution:  2.4Å
Species:  Turkey
References:  73
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human beta1 adrenergic receptor bound to epinephrine and nanobody 6B9
PDB Id:  7BTS
Ligand:  (-)-adrenaline
Resolution:  3.13Å
Species:  Human
References:  90
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human beta1 adrenergic receptor bound to norepinephrine and nanobody 6B9
PDB Id:  7BU6
Ligand:  (-)-noradrenaline
Resolution:  2.7Å
Species:  Human
References:  90
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human beta1 adrenergic receptor bound to BI-167107 and nanobody 6B9
PDB Id:  7BU7
Ligand:  BI-167107
Resolution:  2.6Å
Species:  Human
References:  90
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human beta1 adrenergic receptor bound to carazolol
PDB Id:  7BVQ
Ligand:  carazolol
Resolution:  2.5Å
Species:  Human
References:  90
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
β1-adrenoceptor 55
β2-adrenoceptor 45-46,55,93
α2A-adrenoceptor 89
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
noradrenaline
(-)-noradrenaline
Comments: Noradrenaline exhibits greater potency than adrenaline
Potency order of endogenous ligands (Human)
(-)-noradrenaline > (-)-adrenaline

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
[3H](-)CGP 12177 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Partial agonist 6.6 – 9.9 pKd 5-6,38
⤷ pKd 6.6 – 9.9 [5-6,38]
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 9.4 pKi 5-6,50
⤷ pKi 9.4 [5-6,50]
pindolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 8.6 – 9.3 pKi 6,44
⤷ pKi 8.6 – 9.3 [6,44]
(-)-Ro 363 Small molecule or natural product Hs Agonist 8.0 pKi 59
⤷ pKi 8.0 [59]
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 – 7.9 pKi 6,12
⤷ pKi 7.4 – 7.9 [6,12]
xamoterol Small molecule or natural product Hs Partial agonist 7.0 – 7.2 pKi 5,35
⤷ pKi 7.0 – 7.2 [5,35]
indacaterol Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 6.7 pKi 13
⤷ pKi 6.7 (Ki 1.8x10-7 M) [13]
T-0509 Small molecule or natural product Hs Full agonist 6.6 pKi 74
⤷ pKi 6.6 [74]
prenalterol Small molecule or natural product Hs Partial agonist 6.6 pKi 20,35
⤷ pKi 6.6 [20,35]
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pKi 6
⤷ pKi 6.6 [6]
isoprenaline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 6.1 – 7.0 pKi 6,30,74
⤷ pKi 6.1 – 7.0 [6,30,74]
formoterol Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 6.1 – 6.5 pKi 6,14
⤷ pKi 6.1 – 6.5 [6,14]
noradrenaline Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.0 pKi 30
⤷ pKi 6.0 [30]
(±)-adrenaline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pKi 30
⤷ pKi 6.0 [30]
denopamine Small molecule or natural product Hs Partial agonist 5.8 – 6.1 pKi 6,35,81
⤷ pKi 5.8 – 6.1 [6,35,81]
(-)-noradrenaline 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 5.5 – 6.0 pKi 6,30,34
⤷ pKi 5.5 – 6.0 [6,30,34]
(-)-adrenaline 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 Immunopharmacology Ligand Hs Agonist 5.2 – 6.0 pKi 6,30,34
⤷ pKi 5.2 – 6.0 [6,30,34]
dobutamine Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 5.2 – 5.5 pKi 6,35
⤷ pKi 5.2 – 5.5 [6,35]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.2 pKi 6
⤷ pKi 5.2 [6]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.0 pKi 6
⤷ pKi 5.0 [6]
levosalbutamol Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Partial agonist 4.7 pKi 6
⤷ pKi 4.7 [6]
terbutaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 3.9 pKi 6
⤷ pKi 3.9 [6]
BI-167107 Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.2 pEC50 33,90
⤷ pEC50 9.2 (EC50 6x10-10 M) [33,90]
Description: Determined in an intracellular cAMP accumulation assay in CHO-K1 cells expressing hβ1-AR
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.2 pEC50 6
⤷ pEC50 9.2 [6]
isoprenaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.6 pEC50 6
⤷ pEC50 8.6 [6]
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.4 pEC50 6
⤷ pEC50 8.4 [6]
formoterol Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 8.3 pEC50 6
⤷ pEC50 8.3 [6]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.9 pEC50 6
⤷ pEC50 7.9 [6]
denopamine Small molecule or natural product Hs Partial agonist 7.7 pEC50 6
⤷ pEC50 7.7 [6]
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 7.6 pEC50 6
⤷ pEC50 7.6 [6]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.5 pEC50 6
⤷ pEC50 7.5 [6]
dobutamine Small molecule or natural product Approved drug Hs Partial agonist 6.8 pEC50 6
⤷ pEC50 6.8 [6]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.5 pEC50 6
⤷ pEC50 6.5 [6]
levosalbutamol Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Partial agonist 6.2 pEC50 6
⤷ pEC50 6.2 [6]
terbutaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 5.8 pEC50 6
⤷ pEC50 5.8 [6]
solabegron Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.4 pEC50 83
⤷ pEC50 5.4 [83]
mirabegron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist <4.9 – 5.0 pEC50 25,82
⤷ pEC50 <4.9 – 5.0 [25,82]
abediterol Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 3.62x10-8 M) [3]
Description: Membrane radioligand displacement assay using [3H]CGP12177 as tracer.
Agonist Comments
BI-167107 is a high affinity β1-/β2-AR agonist that has been used to determine agonist bound structures of these β-subtypes [90]. RO-363 is the only β-AR agonist that displays significant selectivity for the β1-AR subtype and has been used experimentally to examine the physiological roles of β1-AR. ICI89406 and LK204-545 are partial agonists with significant β1-AR selectivity [58]. Noradrenaline displays a minor degree of selectivity for β1-AR and is used clinically by slow intravenous infusion to increase the blood pressure associated with shock mainly utilising its actions on α1-AR although the actions on β-AR may help maintain cardiac output. Xamoterol was trialled for the treatment of heart failure being a partial agonist that provided cardiac stimulation yet could block the deleterious effects of high plasma levels of endogenous catecholamines associated with this condition but unfortunately, prolonged stimulation of β1-AR with this compound clearly worsened heart failure and increased mortality so this approach was not successful. Xamoterol, denopamine and dobutamine have varying degrees of β1-AR selectivity and were previously used over short periods to maintain cardiac function in failure. Current clinical uses: noradrenaline and adrenaline are used clinically by slow intravenous infusion to increase the blood pressure associated with shock mainly utilising its actions on α1-AR although the actions on β-AR may help maintain cardiac output.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
bupranolol Small molecule or natural product Approved drug Rn Antagonist 9.0 pA2 63
⤷ pA2 9.0 [63]
atenolol Small molecule or natural product Approved drug Rn Antagonist 6.8 pA2 63
⤷ pA2 6.8 [63]
[125I]ICYP Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.4 – 11.3 pKd 35,39,50,74
⤷ pKd 10.4 – 11.3 (Kd 3.9x10-11 – 4.99x10-12 M) It is necessary to use an excess of a β2-AR-selective ligand such as ICI 118551 in combination with this radioligand in order to allow visualisation of β1-AR binding in native tissue. [35,39,50,74]
cyanopindolol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.4 – 10.5 pKd 6,73
⤷ pKd 10.4 – 10.5 [6,73]
7-methylcyanopindolol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 10.4 pKd 73
⤷ pKd 10.4 [73]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.7 – 10.2 pKd 6,73
⤷ pKd 9.7 – 10.2 [6,73]
[3H](-)CGP 12177 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.2 – 9.4 pKd 5-6,38
⤷ pKd 9.2 – 9.4 3H-CGP12177 (high affinity non-selective antagonist of orthosteric site) is excellent for membrane and whole cell binding with little non-specific binding. [5-6,38]
NDD-825 Small molecule or natural product Rn Antagonist 8.4 pKd 7
⤷ pKd 8.4 [7]
NDD-713 Small molecule or natural product Rn Antagonist 8.1 pKd 7
⤷ pKd 8.1 [7]
bucindolol Small molecule or natural product Hs Antagonist 9.3 pKi 6
⤷ pKi 9.3 [6]
pindolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.6 – 9.7 pKi 6,8,38
⤷ pKi 8.6 – 9.7 [6,8,38]
carvedilol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 – 9.5 pKi 5,22
⤷ pKi 8.8 – 9.5 [5,22]
nebivolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.1 pKi 6
⤷ pKi 9.1 [6]
Description: Radioligand binding
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 – 9.3 pKi 5,38,76
⤷ pKi 8.8 – 9.3 [5,38,76]
ICI-89406 Small molecule or natural product Hs Partial agonist 8.8 pKi 58
⤷ pKi 8.8 [58]
betaxolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.2 – 9.1 pKi 5,50,75
⤷ pKi 8.2 – 9.1 [5,50,75]
timolol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.3 – 9.0 pKi 5,8,38
⤷ pKi 8.3 – 9.0 [5,8,38]
NDD-825 Small molecule or natural product Hs Antagonist 8.3 – 9.0 pKi 7
⤷ pKi 8.3 – 9.0 [7]
CGP 20712A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.8 – 9.2 pKi 5,22,50,73,76
⤷ pKi 7.8 – 9.2 [5,22,50,73,76]
(-)-propranolol Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.9 – 8.9 pKi 5,38,50,76
⤷ pKi 7.9 – 8.9 [5,38,50,76]
NIP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 50
⤷ pKi 8.4 [50]
bunolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 pKi 4
⤷ pKi 8.4 [4]
pKi 8.4 (Ki 3.99x10-9 M) [4]
LK 204-545 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 8.5 pKi 7,50
⤷ pKi 8.2 – 8.5 [7,50]
bupranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.3 – 9.0 pKi 5,22,50
⤷ pKi 7.3 – 9.0 [5,22,50]
NDD-713 Small molecule or natural product Hs Antagonist 7.8 – 8.5 pKi 7
⤷ pKi 7.8 – 8.5 [7]
SR59230A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.6 pKi 5-6,22
⤷ pKi 7.5 – 8.6 [5-6,22]
cicloprolol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.0 pKi 50
⤷ pKi 8.0 [50]
labetalol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.6 – 8.2 pKi 4-5,8
⤷ pKi 7.6 – 8.2 [4-5,8]
bisoprolol Small molecule or natural product Approved drug Hs Antagonist 7.8 pKi 7
⤷ pKi 7.8 (Ki 1x10-8 M) [7]
metoprolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.0 – 7.9 pKi 5,8,22,34,50
⤷ pKi 7.0 – 7.9 [5,8,22,34,50]
atenolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.7 – 7.6 pKi 5,38,50
⤷ pKi 6.7 – 7.6 [5,38,50]
NIHP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 50
⤷ pKi 7.1 [50]
H87/07 Small molecule or natural product Hs Antagonist 7.0 pKi 50
⤷ pKi 7.0 [50]
landiolol Small molecule or natural product Approved drug Hs Antagonist 7.0 pKi 62
⤷ pKi 7.0 [62]
nadolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.9 pKi 22
⤷ pKi 6.9 [22]
esmolol Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 6.7 – 6.9 pKi 4,62
⤷ pKi 6.7 – 6.9 [4,62]
propafenone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.7 pKi 4
⤷ pKi 6.7 (Ki 2.05x10-7 M) [4]
practolol Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 6.1 – 6.8 pKi 5,50
⤷ pKi 6.1 – 6.8 [5,50]
acebutolol Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 6.4 – 6.5 pKi 4-5
⤷ pKi 6.4 – 6.5 [4-5]
sotalol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 5.8 – 6.1 pKi 4-5
⤷ pKi 5.8 – 6.1 [4-5]
nebivolol Small molecule or natural product Approved drug Oc Antagonist 8.1 – 8.7 pIC50 65
⤷ pIC50 8.1 – 8.7 [65]
View species-specific antagonist tables
Antagonist Comments
CGP 12177 is listed as a non-selective partial agonist at the β1-AR. It has now been established that the agonist action of this ligand is a result of action at a non-catecholamine activated site on the β1-AR [11]. This site is resistant to propranolol but is eliminated in β1-AR knockout mice, confirming the site of action as the β1-AR. This site was previously referred to as the β4-AR [38]. At the β1-AR, CGP12177 is a high affinity antagonist of the orthosteric catecholamine conformation. At higher concentrations, it activates a secondary conformation of the β1-AR. This secondary conformation can be activated by several compounds including pindolol, alprenolol, cyanopindolol, carazolol and carvedilol and is relatively resistant to antagonism by many β-antagonists (compared to the catecholamine conformation). Many of the antagonists acting at β1-AR display partial agonist properties including pindolol, carazolol, labetalol, SR59230A, LK 204-545, cyanopindolol, carvedilol and acebutolol [6-7,9] particularly in in vitro assays. Propafenone also primarily blocks α-subunits of sodium ion channels (see the Voltage-gated sodium channels family in the Ion Channels section of this website for further details). Cyanopindolol and 7-methyl cyanopindolol are high affinity antagonists or very weak partial agonists that have been used to explore the relationship between structure and efficacy [73]. CGP20712A is the most selective β1-AR antagonist that is easily available and is widely used in in vitro studies with ≥1000 fold selectivity vs. the other 8 adrenoceptors but does have some off-target activity on other receptors. NDD-713 and NDD-825 are high-affinity, β1-AR selective ligands devoid of agonist activity, off-target effects, and toxicology issues, but with good distribution, metabolism and elimination properties. These ligands are largely devoid of the β2-AR-mediated adverse effects of bronchospasm and vasoconstriction and may be beneficial in patients with cardiovascular and respiratory disease or limb ischemia. Most so-called cardioselective β-AR antagonists display only modest selectivity for β1-AR. Current clinical uses: widely used for heart failure, ischaemic heart disease, cardiac arrythmias, hypertension, glaucoma, portal hypertension, anxiety, migraine, benign essential tremor, thyrotoxicosis, infantile haemangioma (some may target β2-AR as well as β1-AR).
Immunopharmacology Comments
β1-AR is involved in immune regulation and inflammation.
Inflammation: Astrocytes [15] and microglia [79].
Anti-β1-AR autoantibodies: effect on β1-AR conformation and function [19,26], in heart failure [18,28], cardiac fibrosis [51], and cardiomyopathy [51],
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  Stimulation of adenylate cyclase (AC) causes the conversion of ATP into cAMP. This activates protein kinase A, which in turn phosphorylates several substrates, for example L-type Ca2+ channels.
References:  77,88
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Guanylate cyclase stimulation
Other - See Comments
Comments:  ERK1/2 phosphorylation.
Stimulation of guanylate cyclase (GC) causes an increase in cGMP levels, and subsequent activation of protein kinase G.
References:  49,84
Tissue Distribution Click here for help
Heart.
Species:  Human
Technique:  Autoradiography: right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium, atrioventricular node, bundle of His, interatrial and interventricular septa, right atrium, left ventricular free wall, right ventricular free wall, right atrium from an area near the atrioventricular node and cardiac nerves.
References:  21,27,80
Brain: astrocytes.
Species:  Mouse
Technique:  Immunofluorescence and western blot.
References:  15
Lung > brain > spleen > heart, kidney > liver > muscle.
Species:  Mouse
Technique:  Radioligand binding.
References:  2
Intracellular distribution in ventricular myocytes.
Species:  Mouse
Technique:  Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down.
References:  85
Brain: Pineal gland, thalamus, amygdala, septum, hippocampus, anterior basal ganglia.
Species:  Rat
Technique:  Northern blotting.
References:  52
Heart.
Species:  Rat
Technique:  Northern blotting.
References:  52
Subcellular distribution in ventricular myocytes.
Species:  Rat
Technique:  Ca2+ transient and shortening in intact rat ventricular myocytes and acute detubulation to determine localization of surface sarcolemma and t-tubule proteins.
References:  24
Cerebral cortex>WAT>ileum=colon>soleus.
Species:  Rat
Technique:  RT-PCR.
References:  69
Brain: microglia in hippocampus, thalamus and hypothalamus.
Species:  Rat
Technique:  RT-PCR and immunohistochemistry.
References:  79
Heart > lung.
Species:  Rat
Technique:  Radioligand binding.
References:  57,91
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  49
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  57
Myocardium.
Species:  Rat
Technique:  Radioligand binding.
References:  32
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 cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  57
Measurement of cAMP and Ca2+ levels in CHW fibroblast cells endogenously expressing Gs, AC and PKA and transfected with both the β1-adrenoceptor and the L-type Ca2+ channel.
Species:  Human
Tissue:  CHW-1102 fibroblasts.
Response measured:  PTX-insensitive cAMP and Ca2+ accumulation.
References:  92
Measurement of cAMP levels in CHO-K1 cells transfected with the human β1 receptor.
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  cAMP accumulation.
References:  6,34,40,74
Force generation of isolated atrial trabeculae electrically stimulated at 1Hz.
Species:  Human
Tissue:  Atrial trabeculae.
Response measured:  Contraction.
References:  21,40
Relaxation of carbachol-precontracted colon.
Species:  Human
Tissue:  Longitudinal and taenia coli muscle.
Response measured:  Relaxation.
References:  68
Measurement of cAMP in subcellular compartments of living cells.
Species:  Rat
Tissue:  Neonatal ventricular myocytes.
Response measured:  cAMP-sensitive FRET-based sensors.
References:  31
Chronotropic responses in right atria and inotropic responses in left atria.
Species:  Rat
Tissue:  Spontaneously beating right atria and electrically stimulated left atria.
Response measured:  Rate and force of contraction.
References:  43
Relaxation of phenylephrine-precontracted superior mesenteric artery.
Species:  Rat
Tissue:  Superior mesenteric artery.
Response measured:  Relaxation.
References:  63
Physiological Functions Click here for help
All the β-adrenoceptors mediate relaxation of the internal anal sphincter (IAS) smooth muscle, the β1 subtype achieving this via the Gi/o/cGMP pathway.
Species:  Rat
Tissue:  Internal anal sphincter (IAS).
References:  49
Relaxation of colon and oesophagus.
Species:  Mouse
Tissue:  Colon, oesophagus.
References:  64
Tachycardia.
Species:  Mouse
Tissue:  Atrium.
References:  71
Increase in contractile force, positive inotropy.
Species:  Mouse
Tissue:  Right cardiac ventricle.
References:  71
Renin release.
Species:  Human
Tissue:  Kidney.
References:  17
Hypertrophy and apoptosis.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  16,66
Relaxation.
Species:  Human
Tissue:  Colonic longitudinal muscle and taenia coli.
References:  68
Positive inotropic and lusitropic effect.
Species:  Human
Tissue:  Right atrial appendage.
References:  60,80
Neuroinflammatory responses.
Species:  Rat
Tissue:  Microglia.
References:  79
Positive inotropic and chronotropic responses.
Species:  Rat
Tissue:  Right and left atria.
References:  43
Physiological Consequences of Altering Gene Expression Click here for help
β1-adrenoceptor knockout mice exhibit a normal heart rate and blood pressure except during exercise where they have a significantly reduced heart rate but no reduction in maximum exercise capacity or matabolic index.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  72
β1- and β2-adrenoceptor double knockout mice appear to have unaltered basal heart rate, blood pressure and metabolic rate. Stimulation of these receptors by agonists or exercise reveals they exhibit a normal exercise capacity but at a submaximal heart rate.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  70
Most homozygous β1 knockout mice die prenatally, but those that reach adulthood show reduced chronotropic and inotropic responses to β-adrenoceptor agonists and reduced stimulation of adenylyl cyclase in cardiac membrane.
These demonstrate the functional differences between the receptor subtypes, and the importance of the β1-adrenoceptor in mouse development and cardiac function.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  71
In interscapular brown adipose tissue, cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, alpha polypeptide by 3- to 4-fold. Brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT. This effect is eliminated in β1-AR knockout mice.
Species:  Mouse
Tissue:  Brown adipose tissue.
Technique:  Gene targeting in embryonic stem cells.
References:  47
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
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001777 abnormal body temperature regulation PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0002971 abnormal brown adipose tissue morphology PMID: 12161655 
Adrb1tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk
either: (involves: 129/Sv) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2)		 MGI:87937  MP:0001544 abnormal cardiovascular system physiology PMID: 8693001 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0001544 abnormal cardiovascular system physiology PMID: 10358009 
Adrb1tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk
either: (involves: 129/Sv) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2)		 MGI:87937  MP:0008872 abnormal physiological response to xenobiotic PMID: 8693001 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0008872 abnormal physiological response to xenobiotic PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005140 decreased cardiac muscle contractility PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005333 decreased heart rate PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005290 decreased oxygen consumption PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0005290 decreased oxygen consumption PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001260 increased body weight PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0009119 increased brown fat cell size PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0005669 increased circulating leptin level PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0009294 increased interscapular fat pad weight PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0010024 increased total body fat amount PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001261 obese PMID: 12161655 
Adrb1tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk
either: (involves: 129/Sv) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2)		 MGI:87937  MP:0002080 prenatal lethality PMID: 8693001 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Variation in resting heart rate
OMIM: 607276
Role:  Cardiovascular morbidity and mortality risk increased progressively with increasing heart rate
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human S49G Highest mean resting heart rates were seen in individuals with the Ser49Gly polymorphism in ADRB1 67
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A common Gly389 -> Arg polymorphism has been identified in humans.
Although originally thought that Gly389 was the wild-type, both Gly389 and Arg389 are considered to be common.
This polymorphism is located in the intracellular cytoplasmic tail, resulting in differing Gs binding properties.
The Arg398 polymorphism may enhance Gs binding and consequently an increase in adenylyl cyclase activity, although other studies show little difference in antagonist or agonist binding or second messenger signalling. Due to their prevalence, the polymorphisms are not thought to be the primary cause of disease, although may be a small risk factor in common, multi-factorial diseases such as hypertension and atrial fibrillation. They also may alter responses to β-blocker therapy.
Amino acid change:  G389R
References:  1,10,23,37,39,42,54
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A Ser49 -> Gly polymorphism has been identified.
It is associated with a higher resting heart rate in individuals of Chinese/Japanese descent. Ser homozygotes have a more rapid heart rate than Ser/Gly heterozygotes, who have a more rapid heart rate than Gly homozygotes. No difference in molecular pharmacology (antagonist or agonist affinity, efficacy or cell signalling) have been identified when examined in CHO cells.
Amino acid change:  S49G
References:  10,53,67
General Comments
For a review on the β-adrenoceptor polymorphisms see reference [48].

References

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15. Benton KC, Wheeler DS, Kurtoglu B, Ansari MBZ, Cibich DP, Gonzalez DA, Herbst MR, Khursheed S, Knorr RC, Lobner D et al.. (2022) Norepinephrine activates β1 -adrenergic receptors at the inner nuclear membrane in astrocytes. Glia, 70 (9): 1777-1794. [PMID:35589612]

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