Top ▲

α2B-adrenoceptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 26

Nomenclature: α2B-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 7 450 2q11.2 ADRA2B adrenoceptor alpha 2B 42
Mouse 7 450 2 61.95 cM Adra2b adrenergic receptor, alpha 2b 45
Rat 7 453 3q36 Adra2b adrenoceptor alpha 2B 6
Previous and Unofficial Names Click here for help
α2-C2 | ADRA2L1 | ADRA2RL1 | Adrenergic alpha2B- receptor class III | alpha-2B adrenergic receptor | alpha-2B adrenoreceptor | alpha-2BAR | Adra-2b | alpha2B | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb ada2b_human (Hs), ada2b_mouse (Mm), ada2b_rat (Rn)
Other databases
Alphafold P18089 (Hs), P30545 (Mm), P19328 (Rn)
ChEMBL Target CHEMBL1942 (Hs), CHEMBL2405 (Mm), CHEMBL266 (Rn)
DrugBank Target P18089 (Hs), P18089 (Hs), P18089 (Hs)
Ensembl Gene ENSG00000274286 (Hs), ENSMUSG00000058620 (Mm), ENSRNOG00000013887 (Rn)
Entrez Gene 151 (Hs), 11552 (Mm), 24174 (Rn)
Human Protein Atlas ENSG00000274286 (Hs)
KEGG Gene hsa:151 (Hs), mmu:11552 (Mm), rno:24174 (Rn)
OMIM 104260 (Hs)
Pharos P18089 (Hs)
RefSeq Nucleotide NM_000682 (Hs), NM_009633 (Mm), NM_138505 (Rn)
RefSeq Protein NP_000673 (Hs), NP_033763 (Mm), NP_612514 (Rn)
UniProtKB P18089 (Hs), P30545 (Mm), P19328 (Rn)
Wikipedia ADRA2B (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of α2B-AR-GoA complex.
PDB Id:  6K41
Resolution:  2.9Å
Species:  Human
References:  44
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of α2AAR-Gi1 complex.
PDB Id:  6K42
Resolution:  4.1Å
Species:  Human
References:  44
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline
Comments: Adrenaline exhibits similar potency, affinity and efficacy to noradrenaline.

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
[125I]p-iodoclonidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Partial agonist 8.1 pKd 30
⤷ pKd 8.1 [30]
dexmedetomidine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.5 – 9.7 pKi 14,23,28-29,32
⤷ pKi 7.5 – 9.7 [14,23,28-29,32]
clonidine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 6.3 – 9.5 pKi 14,28-29,32
⤷ pKi 6.3 – 9.5 [14,28-29,32]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.5 pKi 26
⤷ pKi 7.5 [26]
lofexidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pKi 10
⤷ pKi 7.2 (Ki 6.77x10-8 M) [10]
Description: Calculated from [3H]RS-79948-197 radioligand competition binding to membrane preparations from CHO cells expressing human α2B-AR.
brimonidine (UK14304) Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Partial agonist 5.5 – 8.3 pKi 14,28-29,32
⤷ pKi 5.5 – 8.3 [14,28-29,32]
guanfacine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 5.8 – 6.5 pKi 14,32
⤷ pKi 5.8 – 6.5 [14,32]
guanabenz Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.0 pKi 32
⤷ pKi 6.0 [32]
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.8 pKi 32
⤷ pKi 5.8 [32]
(±)-adrenaline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.2 – 6.2 pKi 14
⤷ pKi 5.2 – 6.2 [14]
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 5.0 – 6.2 pKi 14,32,40
⤷ pKi 5.0 – 6.2 [14,32,40]
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.2 – 5.7 pKi 14,32
⤷ pKi 5.2 – 5.7 [14,32]
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.4 pKi 32
⤷ pKi 5.4 [32]
(-)-noradrenaline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 3.5 – 6.0 pKi 14,29,32
⤷ pKi 3.5 – 6.0 [14,29,32]
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 4.6 pKi 32
⤷ pKi 4.6 [32]
(-)-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 Full agonist 3.6 – 5.2 pKi 14,32
⤷ pKi 3.6 – 5.2 [14,32]
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 9.2 – 9.9 pEC50 32
⤷ pEC50 9.9 [32]
Description: cAMP generation
pEC50 9.2 [32]
Description: ERK1/2 phosphorylation
A-1262543 Small molecule or natural product Rn Partial agonist 8.4 pEC50 7
⤷ pEC50 8.4 [7]
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.9 – 8.5 pEC50 32
⤷ pEC50 8.5 [32]
Description: ERK1/2 phosphorylation
pEC50 7.9 [32]
Description: cAMP generation
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.6 – 8.5 pEC50 32
⤷ pEC50 8.5 [32]
Description: ERK1/2 phosphorylation
pEC50 7.6 [32]
Description: cAMP generation
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.8 pEC50 32
⤷ pEC50 7.8 [32]
Description: cAMP generation
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.7 pEC50 32
⤷ pEC50 7.7 [32]
Description: cAMP generation
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.4 – 8.0 pEC50 32
⤷ pEC50 8.0 [32]
Description: ERK1/2 phosphorylation
pEC50 7.4 [32]
Description: cAMP generation
brimonidine (UK14304) Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 7.2 – 7.8 pEC50 32
⤷ pEC50 7.8 [32]
Description: ERK1/2 phosphorylation
pEC50 7.2 [32]
Description: cAMP generation
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.9 – 7.8 pEC50 32
⤷ pEC50 7.8 [32]
Description: ERK1/2 phosphorylation
pEC50 6.9 [32]
Description: cAMP generation
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.3 – 7.5 pEC50 32
⤷ pEC50 7.5 [32]
Description: ERK1/2 phosphorylation
pEC50 6.3 [32]
Description: cAMP generation
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.4 – 7.4 pEC50 32
⤷ pEC50 7.4 [32]
Description: ERK1/2 phosphorylation
pEC50 6.4 [32]
Description: cAMP generation
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.5 – 7.1 pEC50 32
⤷ pEC50 7.1 [32]
Description: ERK1/2 phosphorylation
pEC50 6.5 [32]
Description: cAMP generation
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.3 – 7.0 pEC50 32
⤷ pEC50 7.0 [32]
Description: ERK1/2 phosphorylation
pEC50 6.3 [32]
Description: cAMP generation
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 10.9 pIC50 32
⤷ pIC50 10.9 [32]
Description: inhibition of forskolin stimulated cAMP generation
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 9.0 pIC50 32
⤷ pIC50 9.0 [32]
Description: inhibition of forskolin stimulated cAMP generation
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 8.8 pIC50 32
⤷ pIC50 8.8 [32]
Description: inhibition of forskolin stimulated cAMP generation
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.8 pIC50 32
⤷ pIC50 8.8 [32]
Description: inhibition of forskolin stimulated cAMP generation
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.7 pIC50 32
⤷ pIC50 8.7 [32]
Description: inhibition of forskolin stimulated cAMP generation
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 8.6 pIC50 32
⤷ pIC50 8.6 [32]
Description: inhibition of forskolin stimulated cAMP generation
brimonidine (UK14304) Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 8.4 pIC50 32
⤷ pIC50 8.4 [32]
Description: inhibition of forskolin stimulated cAMP generation
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.8 pIC50 32
⤷ pIC50 7.8 [32]
Description: inhibition of forskolin stimulated cAMP generation
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.8 pIC50 32
⤷ pIC50 7.8 [32]
Description: inhibition of forskolin stimulated cAMP generation
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.7 pIC50 32
⤷ pIC50 7.7 [32]
Description: inhibition of forskolin stimulated cAMP generation
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 7.6 pIC50 32
⤷ pIC50 7.6 [32]
Description: inhibition of forskolin stimulated cAMP generation
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.5 pIC50 32
⤷ pIC50 7.5 [32]
Description: inhibition of forskolin stimulated cAMP generation
View species-specific agonist tables
Agonist Comments
[125I]p-iodoclonidine binds to the human α2B receptor with a pKd of 8.1 [30]. Many of the compounds listed as agonists will behave as full or partial agonists depending on the system in which they are studied and tend towards full agonism in recombinant systems with high receptor expression. Rat studies suggest that tizanidine mediates its analgesic effects primarily through the α2B-adrenoceptor [19]. Guanabenz order of affinity is α2A-AR>α2B-AR>α2C-AR [1]. There are currently no selective α2B-AR agonists. Clinical uses: Clonidine is used to treat high blood pressure, guanfacine for ADHD and tizanidine to relieve muscle spasticity. Apraclonidine and brimonidine are used in eye drops to relieve glaucoma. Dexmedetomidine (stereoisomer of medetomidine) and xylazine are used for their hypnotic, anxiolytic and analgesic properties as pre-operatives prior to surgery but they may also be used to control agitation associated with schizophrenia or bipolar disorder. Xylazine has recently emerged in the North American illegal drug markets as a common admixture with synthetic opioids particularly fentanyl and is associated with a marked increase in the number of fatalities associated with drug overdose. While opioid antagonists such as naloxone can rapidly reverse the effects of fentanyl, they do not counteract the sedation, bradycardia and hypotension due to xylazine. The α2-AR antagonist atipamezole is widely used to reverse the effects of xylazine in veterinary medicine but this role has yet to be established in the clinic.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]MK-912 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.9 pKd 40
⤷ pKd 8.9 (Kd 1.36x10-9 M) [40]
[3H]rauwolscine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.1 – 9.2 pKd 4,8,31
⤷ pKd 8.1 – 9.2 [4,8,31]
[3H]RX821002 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.0 – 8.1 pKd 8-9,31
⤷ pKd 8.0 – 8.1 [8-9,31]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 26
⤷ pKi 9.4 [26]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.5 – 9.9 pKi 26,31
⤷ pKi 8.5 – 9.9 [26,31]
RS79948 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.6 pKi 31
⤷ pKi 8.6 [31]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.8 pKi 31,40
⤷ pKi 7.9 – 8.8 [31,40]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 26
⤷ pKi 8.3 [26]
rauwolscine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 40
⤷ pKi 8.3 [40]
yohimbine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.7 – 8.9 pKi 4,9,31,40
⤷ pKi 7.7 – 8.9 [4,9,31,40]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 35
⤷ pKi 8.2 (Ki 5.7x10-9 M) [35]
MK-912 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 31
⤷ pKi 8.2 [31]
RX821002 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.4 pKi 31,40
⤷ pKi 7.5 – 8.4 [31,40]
atipamezole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 31
⤷ pKi 7.9 [31]
ARC-239 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 – 8.6 pKi 4,9,31,40
⤷ pKi 6.8 – 8.6 [4,9,31,40]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 – 8.4 pKi 4,9,31,40
⤷ pKi 6.8 – 8.4 [4,9,31,40]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.6 – 8.3 pKi 4,9,31
⤷ pKi 6.6 – 8.3 [4,9,31]
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.7 – 8.2 pKi 4,9,31
⤷ pKi 6.7 – 8.2 [4,9,31]
phenoxybenzamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.4 – 8.5 pKi 31,41
⤷ pKi 8.5 (Ki 3.5x10-9 M) [41]
pKi 6.4 [31]
Description: Two site binding
imiloxan Small molecule or natural product Rn Antagonist 7.3 pKi 25
⤷ pKi 7.3 [25]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.2 pKi 26
⤷ pKi 7.2 [26]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.9 – 7.5 pKi 26,31
⤷ pKi 6.9 – 7.5 [26,31]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.1 pKi 26
⤷ pKi 7.1 [26]
prazosin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.2 – 7.5 pKi 4,9,31,40
⤷ pKi 6.2 – 7.5 [4,9,31,40]
idazoxan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 31
⤷ pKi 6.4 [31]
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.1 – 6.7 pKi 17,31
⤷ pKi 6.1 – 6.7 [17,31]
BRL 44408 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 – 6.2 pKi 31,40
⤷ pKi 5.4 – 6.2 [31,40]
tolazoline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 5.5 pKi 14
⤷ pKi 5.5 (Ki 3.162x10-6 M) [14]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
View species-specific antagonist tables
Antagonist Comments
Pentoxifylline has phosphodiesterase (PDE) inhibitory action in addition to α2B-AR antagonist activity [36]. Rauwolscine is a stereoisomer of yohimbine. AGN-209419 is an α2-AR antagonist (pKb 8.8 vs. mouse α2B-AR) [22]. The α2-AR antagonist atipamezole is widely used to reverse the effects of xylazine in veterinary medicine but this role has yet to be established in the clinic. Atipamezole and bromocriptine can exhibit partial agonist properties in some systems [32]. There are currently no selective α2B-AR antagonists. Clinical uses: α2B-AR are not specific clinical targets for antagonists.
Allosteric Modulator Comments
5-(N-ethyl-N-isopropyl)-amiloride and chlorobenzyldimethylbenzamil are non-selective, negative allosteric regulators at the α2B receptor [43]. However, no binding affinity data is available for these ligands at this receptor.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Potassium channel
Calcium channel
Other - See Comments
Comments:  ERK1/2 phosphorylation
Inhibition of voltage dependent Ca2+ channels
Augmentation of inwardly rectifying K+ channels
References:  5,20,32,34
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Comments:  The physiological significance of this mechanism is unknown. Although this seems to be a contradiction of the primary transduction mechanism, some α2-AR agonists activate adenylyl cyclase at concentrations higher than those that inhibit adenylyl cyclase - hence biphasic responses can be observed.
References:  11,32,34
Tissue Distribution Click here for help
Spleen = kidney = aorta = lung = skeletal muscle = heart = liver.
Species:  Human
Technique:  RNAse protection of RNA.
References:  12
Kidney >> liver > brain = lung = heart = skeletal muscle.
Absent in aorta and spleen.
Species:  Human
Technique:  RNAse protection of mRNA
References:  3,13
α2B-AR mRNA labeling in spleen, liver and striated muscle.
Species:  Human
Technique:  RNA sequencing.
References:  2
α2B-AR mRNA labeling in thalamus.
Species:  Rat
Technique:  In situ hybridisation.
References:  27,33
α2B-adrenoceptors are expressed in the basolateral, but not apical, membrane of the epithelial cells of renal proximal tubules. α2B-adrenoceptors are not expressed in glomeruli, collecting ducts, or the descending limb of the loop of Henle and vasa recta.
Species:  Rat
Technique:  Immunofluorescence.
References:  37
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 the inhibition of adenylate cyclase activity using intact cell preparations (either native or transfected) using the [3H]adenine prelabeling technique to measure cyclic AMP accumulation.
Species:  Human
Tissue:  NG108 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  5
The signalling and selectivity of α-adrenoceptor agonists for the human α2A-, α2B and α2C-adrenoceptors and comparison with human α1- and β-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2B-AR.
Response measured:  Whole cell [3H]rauwolscine binding, CRE-SPAP gene transcription, [3H]cAMP accumulation, ERK1/2 phosphorylation.
References:  32
The affinity and selectivity of -adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A-, α2B-, and α2C-adrenoceptors and comparison with human α1- and β-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2B-AR.
Response measured:  Whole cell [3H]rauwolscine binding.
References:  31
Physiological Functions Click here for help
Vasoconstiction.
Species:  Mouse
Tissue:  Vascular smooth muscle.
References:  15-16,18,21
CNS behaviours associated with sensorimotor gating and compulsivity.
Species:  Mouse
Tissue:  Brain behaviour associated with disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and OCD.
References:  22
Physiological Consequences of Altering Gene Expression Click here for help
The development of α2B and α2C knock-out mice has shown that these two subtypes are not involved in the central hypotensive response to α2 agonists.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  21
α2B knockout mice are unable to develop salt-induced hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adra2btm1Gsb Adra2btm1Gsb/Adra2btm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:87935  MP:0002161 abnormal fertility/fecundity PMID: 10647009  8670422 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0001712 abnormal placenta development PMID: 12068299 
Adra2btm1Gsb Adra2btm1Gsb/Adra2btm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:87935  MP:0000250 abnormal vasoconstriction PMID: 8670422 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0001718 abnormal yolk sac morphology PMID: 12068299 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0005333 decreased heart rate PMID: 12068299 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0006207 embryonic lethality during organogenesis PMID: 12068299 
Adra2btm1Gsb Adra2btm1Gsb/Adra2btm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:87935  MP:0002082 postnatal lethality PMID: 8670422 
Biologically Significant Variants Click here for help
Type:  Polymorphism
Species:  Human
Description:  Deletion/deletion (DD) genotype of the insertion/deletion polymorphism in the α2B-AR is associated with increased risk of acute coronary events.
References:  38-39

References

Show »

1. 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

2. Basarrate S, Monzel AS, Smith JLM, Marsland AL, Trumpff C, Picard M. (2024) Glucocorticoid and Adrenergic Receptor Distribution Across Human Organs and Tissues: A Map for Stress Transduction. Psychosom Med, 86 (2): 89-98. [PMID:38193786]

3. Blaxall HS, Hass NA, Bylund DB. (1994) Expression of alpha 2-adrenergic receptor genes in rat tissues. Receptor, 4 (3): 191-9. [PMID:7812219]

4. Bylund DB, Blaxall HS, Iversen LJ, Caron MG, Lefkowitz RJ, Lomasney JW. (1992) Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol, 42: 1-5. [PMID:1353247]

5. Bylund DB, Ray-Prenger C. (1989) Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype. J Pharmacol Exp Ther, 251 (2): 640-4. [PMID:2553931]

6. Chen WM, Chang AC, Shie BJ, Chang YH, Chang NC. (1992) Molecular cloning and characterization of a mouse alpha 2C2 adrenoceptor subtype gene. Biochim Biophys Acta, 1171 (2): 219-23. [PMID:1336396]

7. Chu KL, Xu J, Frost J, Li L, Gomez E, Dart MJ, Jarvis MF, Meyer MD, McGaraughty S. (2015) A selective α2 B adrenoceptor agonist (A-1262543) and duloxetine modulate nociceptive neurones in the medial prefrontal cortex, but not in the spinal cord of neuropathic rats. Eur J Pain, 19 (5): 649-60. [PMID:25154730]

8. Deupree JD, Hinton KA, Cerutis DR, Bylund DB. (1996) Buffers differentially alter the binding of [3H]rauwolscine and [3H]RX821002 to the alpha-2 adrenergic receptor subtypes. J Pharmacol Exp Ther, 278 (3): 1215-27. [PMID:8819505]

9. Devedjian JC, Esclapez F, Denis-Pouxviel C, Paris H. (1994) Further characterization of human alpha 2-adrenoceptor subtypes: [3H]RX821002 binding and definition of additional selective drugs. Eur J Pharmacol, 252 (1): 43-9. [PMID:7908642]

10. Diamanti E, Del Bello F, Carbonara G, Carrieri A, Fracchiolla G, Giannella M, Mammoli V, Piergentili A, Pohjanoksa K, Quaglia W et al.. (2012) Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations?. Bioorg Med Chem, 20 (6): 2082-90. [PMID:22341244]

11. Eason MG, Kurose H, Holt BD, Raymond JR, Liggett SB. (1992) Simultaneous coupling of alpha 2-adrenergic receptors to two G-proteins with opposing effects. Subtype-selective coupling of alpha 2C10, alpha 2C4, and alpha 2C2 adrenergic receptors to Gi and Gs. J Biol Chem, 267 (22): 15795-801. [PMID:1322406]

12. Eason MG, Liggett SB. (1993) Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues. Mol Pharmacol, 44 (1): 70-5. [PMID:7688069]

13. Handy DE, Flordellis CS, Bogdanova NN, Bresnahan MR, Gavras H. (1993) Diverse tissue expression of rat alpha 2-adrenergic receptor genes. Hypertension, 21 (6 Pt 1): 861-5. [PMID:7684725]

14. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM. (1998) Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol, 55 (7): 1035-43. [PMID:9605427]

15. Kable JW, Murrin LC, Bylund DB. (2000) In vivo gene modification elucidates subtype-specific functions of alpha(2)-adrenergic receptors. J Pharmacol Exp Ther, 293 (1): 1-7. [PMID:10734146]

16. Kanagy NL. (2005) Alpha(2)-adrenergic receptor signalling in hypertension. Clin Sci (Lond), 109 (5): 431-7. [PMID:16232127]

17. Kennis LE, Bischoff FP, Mertens CJ, Love CJ, Van den Keybus FA, Pieters S, Braeken M, Megens AA, Leysen JE. (2000) New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants. Bioorg Med Chem Lett, 10 (1): 71-4. [PMID:10636247]

18. Knaus AE, Muthig V, Schickinger S, Moura E, Beetz N, Gilsbach R, Hein L. (2007) Alpha2-adrenoceptor subtypes--unexpected functions for receptors and ligands derived from gene-targeted mouse models. Neurochem Int, 51 (5): 277-81. [PMID:17664025]

19. Leiphart JW, Dills CV, Levy RM. (2004) Alpha2-adrenergic receptor subtype specificity of intrathecally administered tizanidine used for analgesia for neuropathic pain. J Neurosurg, 101 (4): 641-7. [PMID:15481719]

20. Limbird LE. (1988) Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. FASEB J, 2 (11): 2686-95. [PMID:2840317]

21. Link RE, Desai K, Hein L, Stevens ME, Chruscinski A, Bernstein D, Barsh GS, Kobilka BK. (1996) Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science, 273 (5276): 803-5. [PMID:8670422]

22. Luhrs L, Manlapaz C, Kedzie K, Rao S, Cabrera-Ghayouri S, Donello J, Gil D. (2016) Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice. Neuroscience, 339: 608-621. [PMID:27751959]

23. MacDonald E, Kobilka BK, Scheinin M. (1997) Gene targeting--homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci, 18 (6): 211-9. [PMID:9227000]

24. Makaritsis KP, Handy DE, Johns C, Kobilka B, Gavras I, Gavras H. (1999) Role of the alpha2B-adrenergic receptor in the development of salt-induced hypertension. Hypertension, 33 (1): 14-7. [PMID:9931075]

25. Michel AD, Loury DN, Whiting RL. (1990) Assessment of imiloxan as a selective alpha 2B-adrenoceptor antagonist. Br J Pharmacol, 99 (3): 560-4. [PMID:1970500]

26. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther, 303 (2): 791-804. [PMID:12388666]

27. Nicholas AP, Pieribone V, Hökfelt T. (1993) Distributions of mRNAs for alpha-2 adrenergic receptor subtypes in rat brain: an in situ hybridization study. J Comp Neurol, 328 (4): 575-94. [PMID:8381444]

28. Peltonen JM, Pihlavisto M, Scheinin M. (1998) Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha2-adrenoceptors. Eur J Pharmacol, 355 (2-3): 275-9. [PMID:9760042]

29. Pihlavisto M, Sjöholm B, Scheinin M, Wurster S. (1998) Modulation of agonist binding to recombinant human alpha2-adrenoceptors by sodium ions. Biochim Biophys Acta, 1448 (1): 135-46. [PMID:9824686]

30. Piletz JE, Zhu H, Chikkala DN. (1996) Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J Pharmacol Exp Ther, 279 (2): 694-702. [PMID:8930173]

31. Proudman RGW, Akinaga J, Baker JG. (2022) The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors. Pharmacol Res Perspect, 10 (2): e00936. [PMID:35224877]

32. Proudman RGW, Akinaga J, Baker JG. (2022) The signaling and selectivity of α-adrenoceptor agonists for the human α2A, α2B and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors. Pharmacol Res Perspect, 10 (5): e01003. [PMID:36101495]

33. Scheinin M, Lomasney JW, Hayden-Hixson DM, Schambra UB, Caron MG, Lefkowitz RJ, Fremeau Jr RT. (1994) Distribution of alpha 2-adrenergic receptor subtype gene expression in rat brain. Brain Res Mol Brain Res, 21 (1-2): 133-49. [PMID:8164514]

34. Scheinin M, Pihlavisto M. (2000) Molecular pharmacology of alpha2-adrenoceptor agonists. Best Practice & Research Clinical Anaesthesiology, 14 (2): 247-260. DOI: 10.1053/bean.2000.00

35. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE. (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl.), 124 (1-2): 57-73. [PMID:8935801]

36. Semmler J, Gebert U, Eisenhut T, Moeller J, Schönharting MM, Alléra A, Endres S. (1993) Xanthine derivatives: comparison between suppression of tumour necrosis factor-alpha production and inhibition of cAMP phosphodiesterase activity. Immunology, 78 (4): 520-5. [PMID:8388363]

37. Shimokawa T, Nakagawa T, Hayashi K, Yamagata M, Yoneda K. (2022) Subcellular distribution of α2-adrenoceptor subtypes in the rodent kidney. Cell Tissue Res, 387 (2): 303-314. [PMID:34837110]

38. Snapir A, Heinonen P, Tuomainen TP, Alhopuro P, Karvonen MK, Lakka TA, Nyyssönen K, Salonen R, Kauhanen J, Valkonen VP et al.. (2001) An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events. J Am Coll Cardiol, 37 (6): 1516-22. [PMID:11345359]

39. Snapir A, Mikkelsson J, Perola M, Penttilä A, Scheinin M, Karhunen PJ. (2003) Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death. J Am Coll Cardiol, 41 (2): 190-4. [PMID:12535806]

40. Uhlén S, Porter AC, Neubig RR. (1994) The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. J Pharmacol Exp Ther, 271 (3): 1558-65. [PMID:7996470]

41. Weinshank RL, Adham N, Macchi M, Olsen MA, Branchek TA, Hartig PR. (1991) Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. J Biol Chem, 266 (33): 22427-35. [PMID:1834671]

42. Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR. (1990) Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor. Mol Pharmacol, 38 (5): 681-8. [PMID:2172775]

43. Wilson AL, Seibert K, Brandon S, Cragoe Jr EJ, Limbird LE. (1991) Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype. Mol Pharmacol, 39 (4): 481-6. [PMID:1850091]

44. Yuan D, Liu Z, Kaindl J, Maeda S, Zhao J, Sun X, Xu J, Gmeiner P, Wang HW, Kobilka BK. (2020) Activation of the α2B adrenoceptor by the sedative sympatholytic dexmedetomidine. Nat Chem Biol, 16 (5): 507-512. [PMID:32152538]

45. Zeng DW, Harrison JK, D'Angelo DD, Barber CM, Tucker AL, Lu ZH, Lynch KR. (1990) Molecular characterization of a rat alpha 2B-adrenergic receptor. Proc Natl Acad Sci USA, 87 (8): 3102-6. [PMID:2158103]

Contributors

Show »

How to cite this page