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 21
Mouse 7 455 2 F1 Adra2b adrenergic receptor, alpha 2b 23
Rat 7 453 3q36 Adra2b adrenoceptor alpha 2B 4
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 Ligand(s)
(-)-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 10,17-18
pKi 7.5 – 9.7 [10,17-18]
clonidine Hs Partial agonist 6.7 – 9.5 pKi 10,17-18
pKi 6.7 – 9.5 [10,17-18]
pergolide Hs Partial agonist 7.5 pKi 16
pKi 7.5 [16]
(-)-noradrenaline Hs Partial agonist 5.6 – 9.1 pKi 10,17-18
pKi 5.6 – 9.1 [10,17-18]
brimonidine Hs Partial agonist 6.0 – 8.3 pKi 10,17-18
pKi 6.0 – 8.3 [10,17-18]
guanfacine Hs Full agonist 5.8 – 6.5 pKi 10
pKi 5.8 – 6.5 [10]
oxymetazoline Hs Partial agonist 5.5 – 6.2 pKi 10,20
pKi 5.5 – 6.2 [10,20]
xylazine Hs Partial agonist 5.7 pKi 10
pKi 5.7 [10]
(±)-adrenaline Hs Partial agonist 5.2 – 6.2 pKi 10
pKi 5.2 – 6.2 [10]
Agonist Comments
[125I]p-iodoclonidine binds to the human α2B receptor with a Kd of 7.8 nM [19].
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 2,5
pKd 9.4 [2,5]
[3H]MK-912 Hs Antagonist 8.9 pKd 20
pKd 8.9 [20]
[3H]RX821002 Hs Antagonist 8.0 – 9.1 pKd 5-6
pKd 8.0 – 9.1 [5-6]
lisuride Hs Antagonist 9.9 pKi 16
pKi 9.9 [16]
terguride Hs Antagonist 9.4 pKi 16
pKi 9.4 [16]
spiroxatrine Hs Antagonist 8.8 pKi 20
pKi 8.8 [20]
yohimbine Hs Antagonist 7.9 – 8.9 pKi 2,6,20
pKi 7.9 – 8.9 [2,6,20]
RX821002 Hs Antagonist 8.4 pKi 20
pKi 8.4 [20]
rauwolscine Hs Antagonist 8.3 pKi 20
pKi 8.3 [20]
roxindole Hs Antagonist 8.3 pKi 16
pKi 8.3 [16]
phentolamine Hs Antagonist 8.2 pKi 2,6
pKi 8.2 [2,6]
chlorpromazine Hs Antagonist 7.2 – 8.3 pKi 2,6
pKi 7.2 – 8.3 [2,6]
ARC-239 Hs Antagonist 6.8 – 8.6 pKi 2,6,20
pKi 6.8 – 8.6 [2,6,20]
WB 4101 Hs Antagonist 7.0 – 8.4 pKi 2,6,20
pKi 7.0 – 8.4 [2,6,20]
bromocriptine Hs Antagonist 7.5 pKi 16
pKi 7.5 [16]
imiloxan Rn Antagonist 7.3 pKi 15
pKi 7.3 [15]
apomorphine Hs Antagonist 7.2 pKi 16
pKi 7.2 [16]
cabergoline Hs Antagonist 7.1 pKi 16
pKi 7.1 [16]
prazosin Hs Antagonist 6.4 – 7.5 pKi 2,6,20
pKi 6.4 – 7.5 [2,6,20]
BRL 44408 Hs Antagonist 6.2 pKi 20
pKi 6.2 [20]
View species-specific antagonist tables
Allosteric Regulator Comments
5-(N-ethyl-N-isopropyl)-amiloride and chlorobenzyldimethylbenzamil are non-selective, negative allosteric regulators at the α2B receptor [22]. 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:  3,12
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  7
Tissue Distribution
Spleen = kidney = aorta = lung = skeletal muscle = heart = liver.
Species:  Human
Technique:  RNAse protection of RNA.
References:  8
Kidney >> liver > brain = lung = heart = skeletal muscle.
Absent in aorta and spleen.
Species:  Human
Technique:  RNAse protection of mRNA
References:  1,9
Expression Datasets

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
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:  3
Physiological Functions
Vasoconstiction.
Species:  Mouse
Tissue:  Vascular smooth muscle.
References:  11,13
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:  13
α2B knock out mice are unable to develop salt-induced hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
Phenotypes, Alleles and Disease Models 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 
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

1. Blaxall HS, Hass NA, Bylund DB. (1994) Expression of α2-adrenergic receptor genes in rat tissues. Receptor4: 191-199. [PMID:7812219]

2. 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]

3. 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: 640-644. [PMID:2553931]

4. 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]

5. 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]

6. 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: 43-49. [PMID:7908642]

7. 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: 15795-15801. [PMID:1322406]

8. 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: 70-75. [PMID:7688069]

9. Handy DE, Flordellis CS, Bogdanova NN, Bresnahan MR, Gavras H. (1993) Diverse tissue expression of rat alpha 2-adrenergic receptor genes. Hypertension.21: 861-865. [PMID:7684725]

10. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SAO, Daunt DA, Bonhaus DW, Eglen RM. (1998) Ligand efficacy and potency at recombinant alpha 2 adrenergic receptors - Agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol.55: 1035-1043. [PMID:9605427]

11. 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: 1-7. [PMID:10734146]

12. Limbird LE. (1988) Receptors linked to inhibition of adenylate cyclase: Additional signaling mechanisms. FASEB J.2: 2686-2695. [PMID:2840317]

13. Link RE, Desai K, Hein L, Stevens ME, Chruscinski A, Bernstein D, Barsh GS, Kobilka BK. (1996) Cardiovascular regulation in mice lacking alpha-2 adrenergic receptor subtypes B and C. Science.273: 803-805. [PMID:8670422]

14. 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]

15. 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]

16. 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]

17. Peltonen JM, Pihlavisto M, Scheinin M. (1998) Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha-2 adrenoceptors. Eur J Pharmacol.355: 275-279. [PMID:9760042]

18. Pihlavisto M, Sjöholm B, Scheinin M, Wurster S. (1998) Modulation of agonist binding to recombinant human alpha-2 adrenoceptors by sodium ions. Biochim Biophys Acta Mol Cell Res.1448: 135-146. [PMID:9824686]

19. 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: 694-702. [PMID:8930173]

20. 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 Ther271: 1558-1565. [PMID:7996470]

21. Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR. (1990) Cloning, expression, and pharmacological characterization of a human α2B-adrenergic receptor. Mol. Pharmacol.38: 681-688. [PMID:2172775]

22. Wilson AL, Seibert K, Brandon S, Cragoe EJ Jr, Limbird LE. (1991) Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype. Mol Pharmacol.39: 481-486. [PMID:1850091]

23. 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: 3102-3106. [PMID:2158103]

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 19/12/2013. Accessed on 23/04/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=26.

Contact us | Print | Back to top | Help
Copyright © 2014 IUPHAR