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β1-adrenoceptor

Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 477 10q24-q26 ADRB1 109
Rat 7 466 1q55 Adrb1 108
Mouse 7 466 19 D2 Adrb1 110
Contents:
Structural Information
Database Links
Selected 3D Structures
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
ChEMBL Target 50 (Hs), 10727 (Mm), 10728 (Rn)
Ensembl ENSG00000043591 (Hs), ENSMUSG00000035283 (Mm), ENSRNOG00000017002 (Rn)
Entrez Gene 153 (Hs), 11554 (Mm), 24925 (Rn)
GeneCards ADRB1 (Hs)
HomoloGene 20171 (Hs)
OMIM 109630 (Hs)
PharmGKB Gene PA38 (Hs)
Protein Ontology (PRO) PRO:000001192 (Hs)
RefSeq Nucleotide NM_000684 (Hs), NM_007419 (Mm), NM_012701 (Rn)
RefSeq Protein NP_000675 (Hs), NP_031445 (Mm), NP_036833 (Rn)
UniGene Hs. 99913 (Hs)
UniProt P08588 (Hs), P34971 (Mm), P18090 (Rn)
Wikipedia β1-adrenoceptor
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the Beta1-Adrenergic G Protein-Coupled Receptor
PDB Id:  2VT4
Ligand:  cyanopindolol
Resolution:  2.7Å
Species:  Turkey
References:  263
Search for other structures on the PDB
Search using keywords: Adrenoceptors beta1-adrenoceptor Search using accession numbers: P18090 || P08588 || P34971
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
(-)-[3H]-CGP 12177 Hs Partial agonist 6.6 – 9.9 pKd 111
CGP 12177 Hs Partial agonist 9.4 pKi 131
xamoterol Hs Partial agonist 7.0 pKi 133
isoprenaline Hs Full agonist 6.6 – 7.0 pKi 123,132
prenalterol Hs Partial agonist 6.6 pKi 133,135
T-0509 Hs Full agonist 6.6 pKi 123
noradrenaline Hs Full agonist 6.0 pKi 132
(±)-adrenaline Hs Full agonist 6.0 pKi 132
denopamine Hs Partial agonist 5.8 pKi 133-134
dobutamine Hs Partial agonist 5.5 pKi 133
Agonist Comments
CGP 12177 is listed as a selective partial agonist at the β1 -adrenoceptor. 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-adrenoceptor. This site is resistant to propanolol but is eliminated in β1-adrenoceptor knockout mice, confirming the site of action as the β1-adrenoceptor. This site was previously referred to as the β4-adrenoceptor. See reference [111] for additional information.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
(-)[125I]ICYP Hs Antagonist 10.0 – 11.3 pKd 123,131,133,137
(-)-[3H]-CGP 12177 Hs Antagonist 6.6 – 9.2 pKd 111,136
carvedilol Hs Antagonist 9.5 pKi 138
CGP 12177 Hs Antagonist 8.8 – 9.3 pKi 111,136
CGP 20712A Hs Antagonist 8.5 – 9.2 pKi 131,136,138
betaxolol Hs Antagonist 8.8 pKi 131
SR59230A Hs Antagonist 8.6 pKi 138
(-)-propranolol Hs Antagonist 8.2 – 8.9 pKi 111,131,136
LK 204-545 Hs Antagonist 8.5 pKi 131
NIP Hs Antagonist 8.4 pKi 131
bupranolol Hs Antagonist 7.3 – 9.0 pKi 131,138
cicloprolol Hs Antagonist 8.0 pKi 131
ICI 118551 Hs Antagonist 7.4 pKi 131
metoprolol Hs Antagonist 7.0 – 7.6 pKi 131,136,138
atenolol Hs Antagonist 6.7 – 7.6 pKi 111,131,136
NIHP Hs Antagonist 7.1 pKi 131
H87/07 Hs Antagonist 7.0 pKi 131
nadolol Hs Antagonist 6.9 pKi 138
practolol Hs Antagonist 6.1 – 6.8 pKi 131,136
Antagonist Comments
CGP 12177 acts as an antagonist at the catecholamine site of the β1-adrenoceptor, in addition to acting as a partial agonist at the second site on the β1-adrenoceptor. For more information see references [111].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate 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:  113-114
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Guanylate cyclase stimulation
Comments:  Stimulation of guanylate cyclase (GC) causes an increase in cGMP levels, and subsequent activation of protein kinase G.
References:  115
Tissue Distribution
Heart > lung.
Species:  Rat
Technique:  Radioligand binding.
References:  122
Brain: Pineal gland, thalamus, amygdala, septum, hippocampus, anterior basal ganglia.
Species:  Rat
Technique:  Northern blotting.
References:  108
Heart.
Species:  Rat
Technique:  Northern blotting.
References:  108
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  115
Lung > brain > spleen > heart, kidney > liver > muscle.
Species:  Mouse
Technique:  Radioligand binding.
References:  126
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  122
Myocardium.
Species:  Rat
Technique:  Radioligand binding.
References:  127
Functional Assays
Measurement of cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  122
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:  123-124
Force generation of isolated atrial trabeculae electrically stimulated at 1Hz.
Species:  Human
Tissue:  Atrial trabeculae.
Response measured:  Contraction.
References:  124
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:  125
Physiological Functions
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:  115
Relaxation of colon and oesophagus.
Species:  Mouse
Tissue:  Colon, oesophagus.
References:  128
Apoptosis.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  129
Tachycardia.
Species:  Mouse
Tissue:  Atrium.
References:  116
Increase in contractile force, positive inotropy.
Species:  Mouse
Tissue:  Right cardiac ventricle.
References:  116
Renin release.
Species:  Human
Tissue:  Kidney.
References:  130
Physiological Consequences of Altering Gene Expression
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:  116
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:  117
β1- and β2-adrenoceptor double knockout mice appear to have unaltered basal heart rate, blood pressure and meatabolic 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:  118
Biologically Significant Variants
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 enhances Gs binding and consequently an increase in adenylyl cyclase activity.
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. They also may result in differing responses to β-blocker therapy.
Type:  Single nucletide polymorphisms.
Species:  Human
References:  119
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.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  120-121
Receptor Comments
For a review on the β-adrenoceptor polymorphisms see reference [112].

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

Richard A. Bond, David B. Bylund, Douglas C. Eikenburg, J. Paul Hieble, Rebecca Hills, Kenneth P. Minneman, Sergio Parra.
Adrenoceptors: β1-adrenoceptor. Last modified on 2010-07-21. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=28.


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