Nomenclature: α2B-adrenoceptor

Family: Adrenoceptors

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

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 450 2p13-q13 ADRA2B adrenoceptor alpha 2B 28
Mouse 7 455 2 F1 Adra2b adrenergic receptor, alpha 2b 30
Rat 7 453 3q36 Adra2b adrenoceptor alpha 2B 5
Previous and Unofficial Names
α2-C2
RNG
ADRA2L1
ADRA2RL1
ADRARL1
adrenergic, alpha-2B-, receptor
Adrenergic alpha2B- receptor class III
Adrenergic, alpha2B-, receptor class III
adrenergic receptor, alpha 2b
alpha-2B adrenergic receptor
alpha-2B adrenoceptor
alpha-2B adrenoreceptor
alpha-2BAR
alpha2B
[a]2B
Adra-2b
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
(-)-adrenaline
(-)-noradrenaline
Comments: Adrenaline exhibits greater relative potency than noradrenaline
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dexmedetomidine Hs Full agonist 7.5 – 9.7 pKi 11,21-22
pKi 7.5 – 9.7 [11,21-22]
clonidine Hs Partial agonist 6.7 – 9.5 pKi 11,21-22
pKi 6.7 – 9.5 [11,21-22]
pergolide Hs Partial agonist 7.5 pKi 20
pKi 7.5 [20]
(-)-noradrenaline Hs Partial agonist 5.6 – 9.1 pKi 11,21-22
pKi 5.6 – 9.1 [11,21-22]
brimonidine Hs Partial agonist 6.0 – 8.3 pKi 11,21-22
pKi 6.0 – 8.3 [11,21-22]
guanfacine Hs Full agonist 5.8 – 6.5 pKi 11
pKi 5.8 – 6.5 [11]
oxymetazoline Hs Partial agonist 5.5 – 6.2 pKi 11,26
pKi 5.5 – 6.2 [11,26]
xylazine Hs Partial agonist 5.7 pKi 11
pKi 5.7 [11]
(±)-adrenaline Hs Partial agonist 5.2 – 6.2 pKi 11
pKi 5.2 – 6.2 [11]
guanabenz Hs Agonist 6.83 pIC50 1
pIC50 6.83 (IC50 1.49x10-7 M) [1]
Agonist Comments
[125I]p-iodoclonidine binds to the human α2B receptor with a Kd of 7.8 nM [23].
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 Affinity Units Reference
[3H]rauwolscine Hs Antagonist 9.4 pKd 3,6
pKd 9.4 [3,6]
[3H]MK-912 Hs Antagonist 8.9 pKd 26
pKd 8.9 [26]
[3H]RX821002 Hs Antagonist 8.0 – 9.1 pKd 6-7
pKd 8.0 – 9.1 [6-7]
lisuride Hs Antagonist 9.9 pKi 20
pKi 9.9 [20]
terguride Hs Antagonist 9.4 pKi 20
pKi 9.4 [20]
spiroxatrine Hs Antagonist 8.8 pKi 26
pKi 8.8 [26]
phenoxybenzamine Hs Antagonist 8.46 pKi 27
pKi 8.46 (Ki 3.5x10-9 M) [27]
yohimbine Hs Antagonist 7.9 – 8.9 pKi 3,7,26
pKi 7.9 – 8.9 [3,7,26]
RX821002 Hs Antagonist 8.4 pKi 26
pKi 8.4 [26]
rauwolscine Hs Antagonist 8.3 pKi 26
pKi 8.3 [26]
roxindole Hs Antagonist 8.3 pKi 20
pKi 8.3 [20]
zotepine Hs Antagonist 8.24 pKi 24
pKi 8.24 (Ki 5.7x10-9 M) [24]
phentolamine Hs Antagonist 8.2 pKi 3,7
pKi 8.2 [3,7]
chlorpromazine Hs Antagonist 7.2 – 8.3 pKi 3,7
pKi 7.2 – 8.3 [3,7]
ARC-239 Hs Antagonist 6.8 – 8.6 pKi 3,7,26
pKi 6.8 – 8.6 [3,7,26]
WB 4101 Hs Antagonist 7.0 – 8.4 pKi 3,7,26
pKi 7.0 – 8.4 [3,7,26]
bromocriptine Hs Antagonist 7.5 pKi 20
pKi 7.5 [20]
imiloxan Rn Antagonist 7.3 pKi 19
pKi 7.3 [19]
apomorphine Hs Antagonist 7.2 pKi 20
pKi 7.2 [20]
cabergoline Hs Antagonist 7.1 pKi 20
pKi 7.1 [20]
prazosin Hs Antagonist 6.4 – 7.5 pKi 3,7,26
pKi 6.4 – 7.5 [3,7,26]
BRL 44408 Hs Antagonist 6.2 pKi 26
pKi 6.2 [26]
tolazoline Hs Antagonist 5.5 pKi 11
pKi 5.5 (Ki 3.162x10-6 M) [11]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
pentoxifylline Hs Antagonist 5.29 pKi 14
pKi 5.29 (Ki 5.18x10-6 M) [14]
mirtazapine Hs Antagonist 6.65 pIC50 13
pIC50 6.65 (IC50 2.239x10-7 M) [13]
View species-specific antagonist tables
Antagonist Comments
Pentoxifylline has phosphodiesterase (PDE) inhibitory action in addition to α2B-adrenoceptor antagonist activity [25].
Allosteric Modulator Comments
5-(N-ethyl-N-isopropyl)-amiloride and chlorobenzyldimethylbenzamil are non-selective, negative allosteric regulators at the α2B receptor [29]. However, no binding affinity data is available for these ligands at this receptor.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
References:  4,16
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  8
Tissue Distribution
Spleen = kidney = aorta = lung = skeletal muscle = heart = liver.
Species:  Human
Technique:  RNAse protection of RNA.
References:  9
Kidney >> liver > brain = lung = heart = skeletal muscle.
Absent in aorta and spleen.
Species:  Human
Technique:  RNAse protection of mRNA
References:  2,10
Expression Datasets

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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]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
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
Vasoconstiction.
Species:  Mouse
Tissue:  Vascular smooth muscle.
References:  12,17
Physiological Consequences of Altering Gene Expression
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
α2B knock out mice are unable to develop salt-induced hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  18
Phenotypes, Alleles and Disease Models 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 
Available Assays
DiscoveRx PathHunter® CHO-K1 ADRA2B β-Arrestin Cell Line (Cat no. 93-0641C2)
PathHunter® eXpress ADRA2B CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0641E2CP2M)
more info

REFERENCES

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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: 219-223. [PMID:1336396]

6. 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: 1215-1227. [PMID:8819505]

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18. 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. Hypertension33: 14-17. [PMID:9931075]

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20. 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 Ther303: 791-804. [PMID:12388666]

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24. 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: 57-73. [PMID:8935801]

25. 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. Immunology78 (4): 520-5. [PMID:8388363]

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To cite this database 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: α2B-adrenoceptor. Last modified on 11/06/2014. Accessed on 30/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=26.

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