Top ▲

β1-adrenoceptor

Click here for help

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

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!
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

Show »

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

Show »

1. Ahles A, Rodewald F, Rochais F, Bünemann M, Engelhardt S. (2015) Interhelical interaction and receptor phosphorylation regulate the activation kinetics of different human β1-adrenoceptor variants. J Biol Chem, 290 (3): 1760-9. [PMID:25451930]

2. André C, Erraji L, Gaston J, Grimber G, Briand P, Guillet JG. (1996) Transgenic mice carrying the human beta 2-adrenergic receptor gene with its own promoter overexpress beta 2-adrenergic receptors in liver. Eur J Biochem, 241 (2): 417-24. [PMID:8917438]

3. Aparici M, Gómez-Angelats M, Vilella D, Otal R, Carcasona C, Viñals M, Ramos I, Gavaldà A, De Alba J, Gras J et al.. (2012) Pharmacological characterization of abediterol, a novel inhaled β(2)-adrenoceptor agonist with long duration of action and a favorable safety profile in preclinical models. J Pharmacol Exp Ther, 342 (2): 497-509. [PMID:22588259]

4. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

5. Baker JG. (2005) The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol, 144 (3): 317-22. [PMID:15655528]

6. Baker JG. (2010) The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br J Pharmacol, 160 (5): 1048-61. [PMID:20590599]

7. Baker JG, Gardiner SM, Woolard J, Fromont C, Jadhav GP, Mistry SN, Thompson KSJ, Kellam B, Hill SJ, Fischer PM. (2017) Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease. FASEB J, 31 (7): 3150-3166. [PMID:28400472]

8. Baker JG, Hall IP, Hill SJ. (2003) Agonist and inverse agonist actions of beta-blockers at the human beta 2-adrenoceptor provide evidence for agonist-directed signaling. Mol Pharmacol, 64 (6): 1357-69. [PMID:14645666]

9. Baker JG, Kemp P, March J, Fretwell L, Hill SJ, Gardiner SM. (2011) Predicting in vivo cardiovascular properties of β-blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses. FASEB J, 25 (12): 4486-97. [PMID:21865315]

10. Baker JG, Proudman RG, Hill SJ. (2013) Impact of polymorphic variants on the molecular pharmacology of the two-agonist conformations of the human β1-adrenoceptor. PLoS One, 8 (11): e77582. [PMID:24250787]

11. Baker JG, Proudman RG, Hill SJ. (2014) Identification of key residues in transmembrane 4 responsible for the secondary, low-affinity conformation of the human β1-adrenoceptor. Mol Pharmacol, 85 (5): 811-29. [PMID:24608857]

12. Baker JG, Proudman RG, Hill SJ. (2015) Salmeterol's extreme β2 selectivity is due to residues in both extracellular loops and transmembrane domains. Mol Pharmacol, 87 (1): 103-20. [PMID:25324048]

13. Beattie D, Beer D, Bradley ME, Bruce I, Charlton SJ, Cuenoud BM, Fairhurst RA, Farr D, Fozard JR, Janus D et al.. (2012) An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterol. Bioorg Med Chem Lett, 22 (19): 6280-5. [PMID:22932315]

14. Beattie D, Bradley M, Brearley A, Charlton SJ, Cuenoud BM, Fairhurst RA, Gedeck P, Gosling M, Janus D, Jones D et al.. (2010) A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilators. Bioorg Med Chem Lett, 20 (17): 5302-7. [PMID:20655218]

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]

16. Berthouze-Duquesnes M, Lucas A, Saulière A, Sin YY, Laurent AC, Galés C, Baillie G, Lezoualc'h F. (2013) Specific interactions between Epac1, β-arrestin2 and PDE4D5 regulate β-adrenergic receptor subtype differential effects on cardiac hypertrophic signaling. Cell Signal, 25 (4): 970-80. [PMID:23266473]

17. Bilezikian JP. (1987) Defining the Role of Adrenergic Receptors in Human Physiology. In Adrenergic Receptors in Man. Edited by Insel PA (Marcel Dekker) 37-68. [ISBN:0824776291]

18. Boivin-Jahns V, Uhland K, Holthoff HP, Beyersdorf N, Kocoski V, Kerkau T, Münch G, Lohse MJ, Ungerer M, Jahns R. (2018) Cyclopeptide COR-1 to treat beta1-adrenergic receptor antibody-induced heart failure. PLoS One, 13 (8): e0201160. [PMID:30125285]

19. Bornholz B, Weidtkamp-Peters S, Schmitmeier S, Seidel CA, Herda LR, Felix SB, Lemoine H, Hescheler J, Nguemo F, Schäfer C et al.. (2013) Impact of human autoantibodies on β1-adrenergic receptor conformation, activity, and internalization. Cardiovasc Res, 97 (3): 472-80. [PMID:23208588]

20. Bristow MR, Hershberger RE, Port JD, Minobe W, Rasmussen R. (1989) Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol, 35 (3): 295-303. [PMID:2564629]

21. Buxton BF, Jones CR, Molenaar P, Summers RJ. (1987) Characterization and autoradiographic localization of beta-adrenoceptor subtypes in human cardiac tissues. Br J Pharmacol, 92 (2): 299-310. [PMID:2823947]

22. Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA, Weber AE. (1999) Potent and selective human beta(3)-adrenergic receptor antagonists. J Pharmacol Exp Ther, 290 (2): 649-55. [PMID:10411574]

23. Chen L, Xiao T, Chen L, Xie S, Deng M, Wu D. (2018) The Association of ADRB1 and CYP2D6 Polymorphisms With Antihypertensive Effects and Analysis of Their Contribution to Hypertension Risk. Am J Med Sci, 355 (3): 235-239. [PMID:29549925]

24. Cros C, Brette F. (2013) Functional subcellular distribution of β1- and β2-adrenergic receptors in rat ventricular cardiac myocytes. Physiol Rep, 1 (3): e00038. [PMID:24303124]

25. Dehvari N, Sato M, Bokhari MH, Kalinovich A, Ham S, Gao J, Nguyen HTM, Whiting L, Mukaida S, Merlin J et al.. (2020) The metabolic effects of mirabegron are mediated primarily by β3 -adrenoceptors. Pharmacol Res Perspect, 8 (5): e00643. [PMID:32813332]

26. Du Y, Yan L, Wang J, Zhan W, Song K, Han X, Li X, Cao J, Liu H. (2012) β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways. PLoS One, 7 (12): e52911. [PMID:23300817]

27. Elnatan J, Molenaar P, Rosenfeldt FL, Summers RJ. (1994) Autoradiographic localization and quantitation of beta 1- and beta 2-adrenoceptors in the human atrioventricular conducting system: a comparison of patients with idiopathic dilated cardiomyopathy and ischemic heart disease. J Mol Cell Cardiol, 26 (3): 313-23. [PMID:7913135]

28. Ernst D, Westerbergh J, Sogkas G, Jablonka A, Ahrenstorf G, Schmidt RE, Heidecke H, Wallentin L, Riemekasten G, Witte T. (2019) Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome. Sci Rep, 9 (1): 14552. [PMID:31601947]

29. Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK. (1987) Cloning of the cDNA for the human β1-adrenergic receptor. Proc Natl Acad Sci USA, 84: 7920-7924. [PMID:2825170]

30. Frielle T, Daniel KW, Caron MG, Lefkowitz RJ. (1988) Structural basis of beta-adrenergic receptor subtype specificity studied with chimeric beta 1/beta 2-adrenergic receptors. Proc Natl Acad Sci USA, 85 (24): 9494-8. [PMID:2849109]

31. Grisan F, Burdyga A, Iannucci LF, Surdo NC, Pozzan T, Di Benedetto G, Lefkimmiatis K. (2020) Studying β1 and β2 adrenergic receptor signals in cardiac cells using FRET-based sensors. Prog Biophys Mol Biol, 154: 30-38. [PMID:31266653]

32. Hancock AA, DeLean AL, Lefkowitz RJ. (1979) Quantitative resolution of beta-adrenergic receptor subtypes by selective ligand binding: application of a computerized model fitting technique. Mol Pharmacol, 16 (1): 1-9. [PMID:39239]

33. Hoenke C, Bouyssou T, Tautermann CS, Rudolf K, Schnapp A, Konetzki I. (2009) Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. Bioorg Med Chem Lett, 19 (23): 6640-4. [PMID:19875286]

34. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN. (2004) Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol, 369 (2): 151-9. [PMID:14730417]

35. Isogaya M, Sugimoto Y, Tanimura R, Tanaka R, Kikkawa H, Nagao T, Kurose H. (1999) Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists. Mol Pharmacol, 56 (5): 875-85. [PMID:10531390]

36. Jasper JR, Link RE, Chruscinski AJ, Kobilka BK, Bernstein D. (1993) Primary structure of the mouse beta 1-adrenergic receptor gene. Biochim Biophys Acta, 1178 (3): 307-9. [PMID:8395893]

37. Jeff JM, Donahue BS, Brown-Gentry K, Roden DM, Crawford DC, Stein CM, Kurnik D. (2014) Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery. Am Heart J, 167 (1): 101-108.e1. [PMID:24332148]

38. Joseph SS, Lynham JA, Colledge WH, Kaumann AJ. (2004) Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers. Naunyn Schmiedebergs Arch Pharmacol, 369 (5): 525-32. [PMID:15060759]

39. Joseph SS, Lynham JA, Grace AA, Colledge WH, Kaumann AJ. (2004) Markedly reduced effects of (-)-isoprenaline but not of (-)-CGP12177 and unchanged affinity of beta-blockers at Gly389-beta1-adrenoceptors compared to Arg389-beta1-adrenoceptors. Br J Pharmacol, 142 (1): 51-6. [PMID:15037517]

40. Joseph SS, Lynham JA, Molenaar P, Grace AA, Colledge WH, Kaumann AJ. (2003) Intrinsic sympathomimetic activity of (-)-pindolol mediated through a (-)-propranolol-resistant site of the beta1-adrenoceptor in human atrium and recombinant receptors. Naunyn Schmiedebergs Arch Pharmacol, 368 (6): 496-503. [PMID:14608456]

41. Jung H, Windhaber R, Palm D, Schnackerz KD. (1995) NMR and circular dichroism studies of synthetic peptides derived from the third intracellular loop of the beta-adrenoceptor. FEBS Lett, 358 (2): 133-6. [PMID:7828722]

42. Kao DP, Davis G, Aleong R, O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA et al.. (2013) Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. Eur J Heart Fail, 15 (3): 324-33. [PMID:23223178]

43. Kompa AR, Summers RJ. (1999) Desensitization and resensitization of beta 1- and putative beta 4-adrenoceptor mediated responses occur in parallel in a rat model of cardiac failure. Br J Pharmacol, 128 (7): 1399-406. [PMID:10602318]

44. Krushinski Jr JH, Schaus JM, Thompson DC, Calligaro DO, Nelson DL, Luecke SH, Wainscott DB, Wong DT. (2007) Indoloxypropanolamine analogues as 5-HT(1A) receptor antagonists. Bioorg Med Chem Lett, 17 (20): 5600-4. [PMID:17804228]

45. Lavoie C, Hébert TE. (2003) Pharmacological characterization of putative beta1-beta2-adrenergic receptor heterodimers. Can J Physiol Pharmacol, 81 (2): 186-95. [PMID:12710533]

46. Lavoie C, Mercier JF, Salahpour A, Umapathy D, Breit A, Villeneuve LR, Zhu WZ, Xiao RP, Lakatta EG, Bouvier M et al.. (2002) Beta 1/beta 2-adrenergic receptor heterodimerization regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy. J Biol Chem, 277 (38): 35402-10. [PMID:12140284]

47. Lee YH, Petkova AP, Konkar AA, Granneman JG. (2015) Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J, 29 (1): 286-99. [PMID:25392270]

48. Leineweber K, Büscher R, Bruck H, Brodde OE. (2004) Beta-adrenoceptor polymorphisms. Naunyn Schmiedebergs Arch Pharmacol, 369 (1): 1-22. [PMID:14647973]

49. Li F, De Godoy M, Rattan S. (2004) Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3-adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle. J Pharmacol Exp Ther, 308 (3): 1111-20. [PMID:14711933]

50. Louis SN, Nero TL, Iakovidis D, Jackman GP, Louis WJ. (1999) LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors. Eur J Pharmacol, 367 (2-3): 431-5. [PMID:10079020]

51. Lv T, Du Y, Cao N, Zhang S, Gong Y, Bai Y, Wang W, Liu H. (2016) Proliferation in cardiac fibroblasts induced by β1-adrenoceptor autoantibody and the underlying mechanisms. Sci Rep, 6: 32430. [PMID:27577254]

52. Machida CA, Bunzow JR, Searles RP, Van Tol H, Tester B, Neve KA, Teal P, Nipper V, Civelli O. (1990) Molecular cloning and expression of the rat beta 1-adrenergic receptor gene. J Biol Chem, 265 (22): 12960-5. [PMID:1695899]

53. Maqbool A, Hall AS, Ball SG, Balmforth AJ. (1999) Common polymorphisms of beta1-adrenoceptor: identification and rapid screening assay. Lancet, 353 (9156): 897. [PMID:10093986]

54. Mason DA, Moore JD, Green SA, Liggett SB. (1999) A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem, 274 (18): 12670-4. [PMID:10212248]

55. Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M. (2002) Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer. J Biol Chem, 277 (47): 44925-31. [PMID:12244098]

56. Miller-Gallacher JL, Nehmé R, Warne T, Edwards PC, Schertler GF, Leslie AG, Tate CG. (2014) The 2.1 Å resolution structure of cyanopindolol-bound β1-adrenoceptor identifies an intramembrane Na+ ion that stabilises the ligand-free receptor. PLoS One, 9 (3): e92727. [PMID:24663151]

57. Minneman KP, Hegstrand LR, Molinoff PB. (1979) The pharmacological specificity of beta-1 and beta-2 adrenergic receptors in rat heart and lung in vitro. Mol Pharmacol, 16 (1): 21-33. [PMID:39243]

58. Mistry SN, Baker JG, Fischer PM, Hill SJ, Gardiner SM, Kellam B. (2013) Synthesis and in vitro and in vivo characterization of highly β1-selective β-adrenoceptor partial agonists. J Med Chem, 56 (10): 3852-65. [PMID:23614528]

59. Molenaar P, Sarsero D, Arch JR, Kelly J, Henson SM, Kaumann AJ. (1997) Effects of (-)-RO363 at human atrial beta-adrenoceptor subtypes, the human cloned beta 3-adrenoceptor and rodent intestinal beta 3-adrenoceptors. Br J Pharmacol, 120 (2): 165-76. [PMID:9117106]

60. Molenaar P, Savarimuthu SM, Sarsero D, Chen L, Semmler AB, Carle A, Yang I, Bartel S, Vetter D, Beyerdörfer I et al.. (2007) (-)-Adrenaline elicits positive inotropic, lusitropic, and biochemical effects through beta2 -adrenoceptors in human atrial myocardium from nonfailing and failing hearts, consistent with Gs coupling but not with Gi coupling. Naunyn Schmiedebergs Arch Pharmacol, 375 (1): 11-28. [PMID:17295024]

61. Moukhametzianov R, Warne T, Edwards PC, Serrano-Vega MJ, Leslie AG, Tate CG, Schertler GF. (2011) Two distinct conformations of helix 6 observed in antagonist-bound structures of a beta1-adrenergic receptor. Proc Natl Acad Sci USA, 108 (20): 8228-32. [PMID:21540331]

62. Nasrollahi-Shirazi S, Sucic S, Yang Q, Freissmuth M, Nanoff C. (2016) Comparison of the β-Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions. J Pharmacol Exp Ther, 359 (1): 73-81. [PMID:27451411]

63. Obara K, Shigematsu M, Takahasi H, Iiboshi Y, Yoshioka K, Kasuya Y, Tanaka Y. (2020) Pharmacological properties of β-adrenoceptors mediating rat superior mesenteric artery relaxation and the effects of chemical sympathetic denervation. Life Sci, 241: 117155. [PMID:31837330]

64. Oostendorp J, Preitner F, Moffatt J, Jimenez M, Giacobino JP, Molenaar P, Kaumann AJ. (2000) Contribution of beta-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wildtype and beta(3)-adrenoceptor knockout mice. Br J Pharmacol, 130 (4): 747-58. [PMID:10864880]

65. Pauwels PJ, Gommeren W, Van Lommen G, Janssen PA, Leysen JE. (1988) The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockers. Mol Pharmacol, 34 (6): 843-51. [PMID:2462161]

66. Pönicke K, Heinroth-Hoffmann I, Brodde OE. (2003) Role of beta 1- and beta 2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol, 367 (6): 592-9. [PMID:12750877]

67. Ranade K, Jorgenson E, Sheu WH, Pei D, Hsiung CA, Chiang FT, Chen YD, Pratt R, Olshen RA, Curb D et al.. (2002) A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet, 70 (4): 935-42. [PMID:11854867]

68. Roberts SJ, Papaioannou M, Evans BA, Summers RJ. (1997) Functional and molecular evidence for beta 1-, beta 2- and beta 3- adrenoceptors in human colon. Br J Pharmacol, 120 (8): 1527-35. [PMID:9113375]

69. Roberts SJ, Papaioannou M, Evans BA, Summers RJ. (1999) Characterization of beta-adrenoceptor mediated smooth muscle relaxation and the detection of mRNA for beta1-, beta2- and beta3-adrenoceptors in rat ileum. Br J Pharmacol, 127 (4): 949-61. [PMID:10433503]

70. Rohrer DK, Chruscinski A, Schauble EH, Bernstein D, Kobilka BK. (1999) Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J Biol Chem, 274 (24): 16701-8. [PMID:10358009]

71. Rohrer DK, Desai KH, Jasper JR, Stevens ME, Regula Jr DP, Barsh GS, Bernstein D, Kobilka BK. (1996) Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects. Proc Natl Acad Sci USA, 93 (14): 7375-80. [PMID:8693001]

72. Rohrer DK, Schauble EH, Desai KH, Kobilka BK, Bernstein D. (1998) Alterations in dynamic heart rate control in the beta 1-adrenergic receptor knockout mouse. Am J Physiol, 274 (4): H1184-93. [PMID:9575921]

73. Sato T, Baker J, Warne T, Brown GA, Leslie AG, Congreve M, Tate CG. (2015) Pharmacological Analysis and Structure Determination of 7-Methylcyanopindolol-Bound β1-Adrenergic Receptor. Mol Pharmacol, 88 (6): 1024-34. [PMID:26385885]

74. Sato Y, Kurose H, Isogaya M, Nagao T. (1996) Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors. Eur J Pharmacol, 315 (3): 363-7. [PMID:8982677]

75. Sharif NA, Xu SX, Crider JY, McLaughlin M, Davis TL. (2001) Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes. J Ocul Pharmacol Ther, 17 (4): 305-17. [PMID:11572462]

76. Soave M, Stoddart LA, Brown A, Woolard J, Hill SJ. (2016) Use of a new proximity assay (NanoBRET) to investigate the ligand-binding characteristics of three fluorescent ligands to the human β1-adrenoceptor expressed in HEK-293 cells. Pharmacol Res Perspect, 4 (5): e00250. [PMID:27588207]

77. Stiles GL, Caron MG, Lefkowitz RJ. (1984) Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev, 64 (2): 661-743. [PMID:6143332]

78. Su M, Zhu L, Zhang Y, Paknejad N, Dey R, Huang J, Lee MY, Williams D, Jordan KD, Eng ET et al.. (2020) Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β1-Adrenergic Receptor. Mol Cell, 80 (1): 59-71.e4. [PMID:32818430]

79. Sugama S, Takenouchi T, Hashimoto M, Ohata H, Takenaka Y, Kakinuma Y. (2019) Stress-induced microglial activation occurs through β-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation. J Neuroinflammation, 16 (1): 266. [PMID:31847911]

80. Summers RJ, Molnaar P, Russell F, Elnatan J, Jones CR, Buxton BF, Chang V, Hambley J. (1989) Coexistence and localization of beta 1- and beta 2-adrenoceptors in the human heart. Eur Heart J, 10 Suppl B: 11-21. [PMID:2553407]

81. Suzuki T, Nantel F, Bonin H, Valiquette M, Bouvier M. (1993) Cellular characterization of the pharmacological selectivity and tachyphylactic properties of denopamine for the human beta adrenergic receptors. J Pharmacol Exp Ther, 267 (2): 785-90. [PMID:7902433]

82. Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, Sasamata M, Miyata K, Uchida H, Yamaguchi O. (2007) Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther, 321 (2): 642-7. [PMID:17293563]

83. Uehling DE, Shearer BG, Donaldson KH, Chao EY, Deaton DN, Adkison KK, Brown KK, Cariello NF, Faison WL, Lancaster ME et al.. (2006) Biarylaniline phenethanolamines as potent and selective beta3 adrenergic receptor agonists. J Med Chem, 49 (9): 2758-71. [PMID:16640337]

84. Wang J, Hanada K, Staus DP, Makara MA, Dahal GR, Chen Q, Ahles A, Engelhardt S, Rockman HA. (2017) Gαi is required for carvedilol-induced β1 adrenergic receptor β-arrestin biased signaling. Nat Commun, 8 (1): 1706. [PMID:29167435]

85. Wang Y, Shi Q, Li M, Zhao M, Reddy Gopireddy R, Teoh JP, Xu B, Zhu C, Ireton KE, Srinivasan S et al.. (2021) Intracellular β1-Adrenergic Receptors and Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation to Enhance Cardiac Contractility. Circ Res, 128 (2): 246-261. [PMID:33183171]

86. Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, Leslie AG, Schertler GF, Tate CG. (2011) The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor. Nature, 469 (7329): 241-4. [PMID:21228877]

87. Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AG, Tate CG, Schertler GF. (2008) Structure of a beta1-adrenergic G-protein-coupled receptor. Nature, 454 (7203): 486-91. [PMID:18594507]

88. Wenzel-Seifert K, Liu HY, Seifert R. (2002) Similarities and differences in the coupling of human beta1- and beta2-adrenoceptors to Gs(alpha) splice variants. Biochem Pharmacol, 64 (1): 9-20. [PMID:12106601]

89. Xu J, He J, Castleberry AM, Balasubramanian S, Lau AG, Hall RA. (2003) Heterodimerization of alpha 2A- and beta 1-adrenergic receptors. J Biol Chem, 278 (12): 10770-7. [PMID:12529373]

90. Xu X, Kaindl J, Clark MJ, Hübner H, Hirata K, Sunahara RK, Gmeiner P, Kobilka BK, Liu X. (2021) Binding pathway determines norepinephrine selectivity for the human β1AR over β2AR. Cell Res, 31 (5): 569-579. [PMID:33093660]

91. Yamada S, Niiya R, Ito Y, Kato Y, Onoue S. (2022) Comparative characterization of β-adrenoceptors in the bladder, heart, and lungs of rats: Alterations in spontaneously hypertensive rats. J Pharmacol Sci, 148 (1): 51-55. [PMID:34924129]

92. Yatani A, Tajima Y, Green SA. (1999) Coupling of beta-adrenergic receptors to cardiac L-type Ca2+ channels: preferential coupling of the beta1 versus beta2 receptor subtype and evidence for PKA-independent activation of the channel. Cell Signal, 11 (5): 337-42. [PMID:10376806]

93. Zhu WZ, Chakir K, Zhang S, Yang D, Lavoie C, Bouvier M, Hébert TE, Lakatta EG, Cheng H, Xiao RP. (2005) Heterodimerization of beta1- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility. Circ Res, 97 (3): 244-51. [PMID:16002745]

Contributors

Show »

How to cite this page