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α2B-adrenoceptor

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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 31
Mouse 7 450 2 61.95 cM Adra2b adrenergic receptor, alpha 2b 33
Rat 7 453 3q36 Adra2b adrenoceptor alpha 2B 5
Previous and Unofficial Names Click here for help
α2-C2 | ADRA2L1 | ADRA2RL1 | alpha-2BAR | Adrenergic alpha2B- receptor class III | alpha-2B adrenergic receptor | alpha-2B adrenoreceptor | 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)
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline
Comments: Adrenaline exhibits greater relative potency than 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
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 12,18,22-23,26
⤷ pKi 7.5 – 9.7 [12,18,22-23,26]
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 6.7 – 9.5 pKi 12,22-23,26
⤷ pKi 6.7 – 9.5 [12,22-23,26]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.5 pKi 21
⤷ pKi 7.5 [21]
lofexidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pKi 8
⤷ pKi 7.2 (Ki 6.77x10-8 M) [8]
Description: Calculated from [3H]RS-79948-197 radioligand competition binding to membrane preparations from CHO cells expressing human α2B-AR.
brimonidine 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 6.0 – 8.3 pKi 12,22-23,26
⤷ pKi 6.0 – 8.3 [12,22-23,26]
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 12,26
⤷ pKi 5.8 – 6.5 [12,26]
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 5.5 – 6.2 pKi 12,26,29
⤷ pKi 5.5 – 6.2 [12,26,29]
(-)-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 Partial agonist 5.4 – 6.0 pKi 12,23,26
⤷ pKi 5.4 – 6.0 [12,23,26]
(±)-adrenaline Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.2 – 6.2 pKi 12
⤷ pKi 5.2 – 6.2 [12]
xylazine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.7 pKi 12
⤷ pKi 5.7 [12]
(-)-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 pKi 12,26
⤷ pKi 5.2 [12,26]
guanabenz Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.8 pIC50 1,26
⤷ pIC50 6.8 (IC50 1.49x10-7 M) [1,26]
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist - - 26
⤷ [26]
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist - - 26
⤷ [26]
Agonist Comments
[125I]p-iodoclonidine binds to the human α2B receptor with a Kd of 7.8 nM [24].
Rat studies suggest that tizanidine mediates its analgesic effects primarily through the α2B-adrenoceptor [15].
As an endogenous ligand, (-)-noradrenaline has intrinsic activity across the adrenoceptor family, but we've only tagged α2B and α2C subtypes as primary drug target as the drug has highest affinity at these isoforms.
Guanabenz order of affinity is α2A-AR>α2B-AR>α2C-AR [1].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]rauwolscine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.4 pKd 3,6
⤷ pKd 9.4 [3,6]
[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 29
⤷ pKd 8.9 (Kd 1.36x10-9 M) [29]
[3H]RX821002 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.0 – 9.1 pKd 6-7
⤷ pKd 8.0 – 9.1 [6-7]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 21
⤷ pKi 9.4 [21]
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 21,25
⤷ pKi 8.5 – 9.9 [21,25]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 pKi 29
⤷ pKi 8.8 [29]
phenoxybenzamine Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.5 pKi 30
⤷ pKi 8.5 (Ki 3.5x10-9 M) [30]
yohimbine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.9 pKi 3,7,25,29
⤷ pKi 7.9 – 8.9 [3,7,25,29]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 21
⤷ pKi 8.3 [21]
rauwolscine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 29
⤷ pKi 8.3 [29]
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 27
⤷ pKi 8.2 (Ki 5.7x10-9 M) [27]
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.2 pKi 3,7
⤷ pKi 8.2 [3,7]
RX821002 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 8.4 pKi 25,29
⤷ pKi 7.5 – 8.4 [25,29]
atipamezole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 25
⤷ pKi 7.9 [25]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.2 – 8.3 pKi 3,7
⤷ pKi 7.2 – 8.3 [3,7]
ARC-239 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.8 – 8.6 pKi 3,7,25,29
⤷ pKi 6.8 – 8.6 [3,7,25,29]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 – 8.4 pKi 3,7,29
⤷ pKi 7.0 – 8.4 [3,7,29]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.5 pKi 21
⤷ pKi 7.5 [21]
imiloxan Small molecule or natural product Rn Antagonist 7.3 pKi 20
⤷ pKi 7.3 [20]
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 21
⤷ pKi 7.2 [21]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.1 pKi 21
⤷ pKi 7.1 [21]
prazosin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.4 – 7.5 pKi 3,7,29
⤷ pKi 6.4 – 7.5 [3,7,29]
idazoxan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 25
⤷ pKi 6.4 [25]
BRL 44408 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 29
⤷ pKi 6.2 [29]
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 12
⤷ pKi 5.5 (Ki 3.162x10-6 M) [12]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.7 pIC50 14
⤷ pIC50 6.7 (IC50 2.239x10-7 M) [14]
View species-specific antagonist tables
Antagonist Comments
Pentoxifylline has phosphodiesterase (PDE) inhibitory action in addition to α2B-adrenoceptor antagonist activity [28].
Allosteric Modulator Comments
5-(N-ethyl-N-isopropyl)-amiloride and chlorobenzyldimethylbenzamil are non-selective, negative allosteric regulators at the α2B receptor [32]. 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 Adenylyl cyclase inhibition
Potassium channel
Calcium channel
References:  4,16
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  9
Tissue Distribution Click here for help
Spleen = kidney = aorta = lung = skeletal muscle = heart = liver.
Species:  Human
Technique:  RNAse protection of RNA.
References:  10
Kidney >> liver > brain = lung = heart = skeletal muscle.
Absent in aorta and spleen.
Species:  Human
Technique:  RNAse protection of mRNA
References:  2,11
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of 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:  4
Physiological Functions Click here for help
Vasoconstiction.
Species:  Mouse
Tissue:  Vascular smooth muscle.
References:  13,17
Physiological Consequences of Altering Gene Expression Click here for help
α2B knock out mice are unable to develop salt-induced hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  19
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:  17
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
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 

References

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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

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4. 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]

5. 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]

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12. 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]

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21. 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]

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