image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

β2-adrenoceptor

Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 413 5q31-q32 ADRB2 140
Rat 7 418 18q12.1 Adrb2 139
Mouse 7 418 18 E1 Adrb2 141
Contents:
Structural Information
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
ChEMBL Target 43 (Hs), 10283 (Mm), 17052 (Rn)
Ensembl ENSG00000169252 (Hs), ENSMUSG00000045730 (Mm), ENSRNOG00000019217 (Rn)
Entrez Gene 154 (Hs), 11555 (Mm), 24176 (Rn)
GeneCards ADRB2 (Hs)
HomoloGene 30948 (Hs)
OMIM 109690 (Hs)
PharmGKB Gene PA39 (Hs)
Protein Ontology (PRO) PRO:000001193 (Hs)
RefSeq Nucleotide NM_000024 (Hs), NM_007420 (Mm), NM_012492 (Rn)
RefSeq Protein NP_000015 (Hs), NP_031446 (Mm), NP_036624 (Rn)
UniGene Hs. 2551 (Hs)
UniProt P07550 (Hs), P18762 (Mm), P10608 (Rn)
Wikipedia β2-adrenoceptor
Search for 3D structures on the PDB
Search using keywords: Adrenoceptors beta2-adrenoceptor Search using accession numbers: P10608 || P07550 || P18762
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
salmeterol Hs Full agonist 8.8 pKi 136
fenoterol Hs Full agonist 6.9 pKi 159
isoprenaline Hs Full agonist 6.4 pKi 123
dobutamine Hs Partial agonist 6.2 pKi 160
(±)-adrenaline Hs Full agonist 6.2 pKi 159
salbutamol Hs Partial agonist 5.8 – 6.1 pKi 133,136
ephedrine Hs Partial agonist 5.6 pKi 159
terbutaline Hs Partial agonist 5.6 pKi 136
noradrenaline Hs Full agonist 5.4 pKi 160
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 10.7 – 11.1 pKd 123,131
timolol Hs Antagonist 9.7 pKi 136
carvedilol Hs Antagonist 9.4 – 9.9 pKi 136,138
CGP 12177 Hs Antagonist 9.4 pKi 131,136
ICI 118551 Hs Inverse agonist 9.2 – 9.5 pKi 131,136,161
CGP 20712A Hs Antagonist 9.3 pKi 136
propranolol Hs Antagonist 9.1 – 9.5 pKi 131,133,136,161
SR59230A Hs Antagonist 9.3 pKi 138
alprenolol Hs Antagonist 9.0 pKi 136
bupranolol Hs Antagonist 8.3 – 9.1 pKi 131,138
nadolol Hs Antagonist 7.0 – 8.6 pKi 136,138
NIP Hs Antagonist 7.5 pKi 131
betaxolol Hs Antagonist 7.2 pKi 131
metoprolol Hs Antagonist 6.3 pKi 131
cicloprolol Hs Antagonist 6.2 pKi 131
NIHP Hs Antagonist 6.0 pKi 131
atenolol Hs Antagonist 5.6 – 6.0 pKi 131,136
LK 204-545 Hs Antagonist 5.2 pKi 131
Allosteric Regulators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
Zn2+ Hs Positive 5.3 pKi 142-143
Zn2+ Hs Negative 3.3 pKi 142-143
Allosteric Regulator Comments
Zn2+ appears to have both positive and negative effects on agonist affinity. At low concentrations it appears to enhance agonist affinity and agonist-stimulated cAMP accumulation. At high concentrations Zn2+ inhibits agonist binding but slows antagonist dissociation [142-143].
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:  113-115,144
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
Lung > heart.
Species:  Rat
Technique:  Radioligand binding.
References:  122
Lung >> skeletal muscle > spleen > kidney > heart > brain > liver.
Species:  Mouse
Technique:  in situ hybridisation.
References:  126
Lung >> spleen > kidney > heart > brain > skeletal muscle > liver.
Species:  Mouse
Technique:  Radioligand binding.
References:  126
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  122
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  115
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 expressing the human β2 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  cAMP accumulation.
References:  123
Measurement of cAMP levels in human lung epithelial cell lines.
Species:  Human
Tissue:  Calu-3 and 16HBE14o- cell lines.
Response measured:  cAMP accumulation.
References:  153
Measurement of cAMP levels in a human macrophage cell line.
Species:  Human
Tissue:  U937 cells.
Response measured:  cAMP accumulation.
References:  154
Measurement of LPS-induced cytokine release (TNFα and Il-10) from human U937 macrophage cells when treated with a β2-adrenoceptor agoinist.
Species:  Human
Tissue:  U937 cells.
Response measured:  Inhibition of TNFα release, stimulation of Il-10 release.
References:  154
Measurement of cAMP levels in Sf9 insect cells transfected with the human β2-adrenoceptor.
Species:  Human
Tissue:  Sf9 cells.
Response measured:  cAMP accumulation.
References:  144
The trachea of an anesthetized mouse is intubated and airway resistance is measured in response to intravenously injected agonists.
Species:  Mouse
Tissue:  Lung.
Response measured:  Decrease in airway resistance.
References:  155
Measurement of cAMP and Ca2+ levels in CHW fibroblast cells endogenously expressing Gs, AC and PKA and transfected with both the β2-adrenoceptor and the L-type Ca2+ channel.
Species:  Human
Tissue:  CHW-1102 fibroblast cells.
Response measured:  PTX-insensitive cAMP and Ca2+ accumulation.
References:  125
Physiological Functions
Stimulation of aqueous humor formation and outflow.
Species:  Human
Tissue:  Eye.
References:  157
Uterine relaxation.
Species:  Human
Tissue:  Myometrial muscle.
References:  158
All the β-adrenoceptors mediate relaxation of the internal anal sphincter (IAS) smooth muscle, the β2 subtype achieving this via both the Gs/cAMP pathway and the Gi/o/cGMP pathway.
Species:  Rat
Tissue:  Internal anal sphincter (IAS) smooth muscle.
References:  115
Inhibition of apoptosis via a PTX-sensitive G-protein.
Apoptosis via Gs and adenylyl cyclase.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  129
Hypotension, lowering of blood pressure.
Species:  Mouse
Tissue:  Blood vessels.
References:  146
Presynaptic facilitation of noradrenlaine release from sympathetic nerves.
Species:  Rat
Tissue:  Isolated perfused kidney.
References:  156
Bronchodilation.
Species:  Mouse
Tissue:  Lung.
References:  155
Physiological Consequences of Altering Gene Expression
Studies involving mice overexpressing the β2-adrenoceptor show alterations in heart beat and contractile response.
Species:  Human
Tissue: 
Technique:  Transgenesis.
References:  145
Studies involving β2-adrenoceptor knockouts have only shown obvious physiological changes when under cardiovascular stress conditions. This subtype is thought not to be involved in postnatal development but does mediate peripheral vascular resistance and energy metabolism.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  146
Transgenic (TG) mice overexpressing the β2-adrenoceptor in airway smooth muscle exhibit enhanced β2 signalling and an increase in basal cAMP levels. Tracheal rings from the TG mice showed increased relaxation to a β-agonist, and in vivo studies showed resistance to methacholine-induced bronchoconstriction.
Overall, a decrease in bronchial hyperresponsiveness was seen in the TG mice: an anti-asthmatic state.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  147
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:  118
Biologically Significant Variants
An Arg16 -> Gly polymorphism has been identified in humans, shown to depress receptor function due to increased receptor downregulation. Studies have suggested this variant may influence vasodilator responses through differences in nitric oxide generation.
In two populations of non-nocturnal and nocturnal asthmatic patients, the presence of the Arg16 -> Gly polymorphism was statistically significantly increased in the nocturnal asthmatic population. This patient population also appeared to be more susceptible to desensitization of the airways to β2-adrenoceptor agonists.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  148-150
A Gln27 -> Glu polymorphism has been identified in humans and found to cause increased isoprenaline-induced vasodilation, suggesting a role in determining vascular reactivity.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  151
A Thr164 -> Ile polymorphism has been identified in humans. To understand the physiological consequences of this variant, a study has been undertaken where the Thr164 -> Ile polymorphism is mimicked in transgenic mice. Results showed impaired receptor coupling to adenylyl cyclase in myocardial membranes in vitro and impaired receptor-mediated cardiac function in vivo.
Type:  Single nucleotide polymorphism.
Species:  Mouse
References:  152
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: β2-adrenoceptor. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=29.


Contact us | Print | Back to top | Help