Nomenclature: α2C-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 7 462 4p16 ADRA2C adrenoceptor alpha 2C 28
Mouse 7 458 5 B2 Adra2c adrenergic receptor, alpha 2c 20
Rat 7 458 14q21 Adra2c adrenoceptor alpha 2C 11
Previous and Unofficial Names
α2-C4
ADRA2L2
ADRA2RL2
ADRARL2
adrenergic, alpha-2C-, receptor
Adrenergic alpha2C- receptor class I
Adrenergic, alpha2C-, receptor class I
adrenergic receptor, alpha 2c
alpha-2 adrenergic receptor subtype C4
alpha-2C adrenergic receptor
alpha-2C adrenoceptor
alpha-2C adrenoreceptor
alpha-2CAR
subtype alpha2-C4
alpha2-C4
alpha2C
[a]2C
Adra-2c
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 7.0 – 9.3 pKi 16,24,26
pKi 7.0 – 9.3 [16,24,26]
apraclonidine Hs Agonist 7.52 pKi 23
pKi 7.52 (Ki 3x10-8 M) [23]
(-)-noradrenaline Hs Full agonist 5.9 – 8.7 pKi 16,24,26
pKi 5.9 – 8.7 [16,24,26]
pergolide Hs Partial agonist 7.2 pKi 22
pKi 7.2 [22]
clonidine Hs Partial agonist 6.0 – 7.8 pKi 16,24,26
pKi 6.0 – 7.8 [16,24,26]
oxymetazoline Hs Partial agonist 6.7 pKi 16,30
pKi 6.7 [16,30]
brimonidine Hs Partial agonist 5.7 – 7.6 pKi 16,24,26
pKi 5.7 – 7.6 [16,24,26]
(±)-adrenaline Hs Full agonist 5.8 – 6.2 pKi 16
pKi 5.8 – 6.2 [16]
guanfacine Hs Partial agonist 5.4 – 6.2 pKi 16
pKi 5.4 – 6.2 [16]
xylazine Hs Partial agonist 4.8 – 5.9 pKi 16
pKi 4.8 – 5.9 [16]
guanabenz Hs Agonist 5.96 pIC50 1
pIC50 5.96 (IC50 1.106x10-6 M) [1]
Agonist Comments
[125I]p-iodoclonidine binds to the human α2C receptor with a Kd of 1.3 nM [27].
Apraclonidine is an approved drug agonist of α2-adrenoceptors [23].
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
JP1302 Hs Antagonist 7.8 pKB 29
pKB 7.8 [29]
[3H]MK-912 Hs Antagonist 10.1 pKd 30
pKd 10.1 [30]
[3H]rauwolscine Hs Antagonist 9.9 pKd 3,5
pKd 9.9 [3,5]
[3H]RX821002 Hs Antagonist 8.2 – 9.2 pKd 5-6
pKd 8.2 – 9.2 [5-6]
lisuride Hs Antagonist 9.9 pKi 22
pKi 9.9 [22]
terguride Hs Antagonist 9.1 pKi 22
pKi 9.1 [22]
rauwolscine Hs Antagonist 9.1 pKi 30
pKi 9.1 [30]
yohimbine Hs Antagonist 8.5 – 9.5 pKi 3,6,30
pKi 8.5 – 9.5 [3,6,30]
spiroxatrine Hs Antagonist 9.0 pKi 30
pKi 9.0 [30]
WB 4101 Hs Antagonist 8.4 – 9.4 pKi 3,6,30
pKi 8.4 – 9.4 [3,6,30]
roxindole Hs Antagonist 8.8 pKi 22
pKi 8.8 [22]
RX821002 Hs Antagonist 8.7 pKi 30
pKi 8.7 [30]
lurasidone Hs Antagonist 7.97 pKi 15
pKi 7.97 (Ki 1.08x10-8 M) [15]
phentolamine Hs Antagonist 7.6 – 7.9 pKi 3,6
pKi 7.6 – 7.9 [3,6]
all-trans-4-oxo-retinoic acid Hs Antagonist 7.74 pKi 10
pKi 7.74 (Ki 1.8x10-8 M) [10]
mirtazapine Hs Antagonist 7.74 pKi 10
pKi 7.74 (Ki 1.8x10-8 M) [10]
Description: Inhibition of [3H]rauwolscine binding.
cabergoline Hs Antagonist 7.7 pKi 22
pKi 7.7 [22]
bromocriptine Hs Antagonist 7.6 pKi 22
pKi 7.6 [22]
ARC-239 Hs Antagonist 6.7 – 8.4 pKi 3,6,30
pKi 6.7 – 8.4 [3,6,30]
apomorphine Hs Antagonist 7.4 pKi 22
pKi 7.4 [22]
prazosin Hs Antagonist 6.7 – 8.0 pKi 3,6,30
pKi 6.7 – 8.0 [3,6,30]
piribedil Hs Antagonist 7.2 pKi 22
pKi 7.2 [22]
chlorpromazine Hs Antagonist 6.9 – 7.4 pKi 3,6
pKi 6.9 – 7.4 [3,6]
BRL 44408 Hs Antagonist 6.8 pKi 30
pKi 6.8 [30]
tolazoline Hs Antagonist 5.43 pKi 16
pKi 5.43 (Ki 3.715x10-6 M) [16]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
mirtazapine Hs Antagonist 6.7 pIC50 18
pIC50 6.7 (IC50 1.995x10-7 M) [18]
Antagonist Comments
Mirtazapine is an antagonist of α2-adrenoceptors and serotonin 5-HT2a and 5-HT2c receptors.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
References:  4,19
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  8
Tissue Distribution
Brain = kidney > aorta = lung = skeletal muscle = heart = spleen.
Absent in the liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  9,25
Brain >> kidney.
Absent in spleen, aorta, heart, liver, lung, skeletal muscle.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  2,13
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
Measurment of adenylate cyclase activity. This assay is done intact cell preparations (either native or transfected) using the [3H]adenine prelabeling technique to measure cAMP accumulation.
Species:  Human
Tissue: 
Response measured:  Inhibition of cAMP accumulation.
References:  4
Isometric contraction is measured with rings of human saphenous veins (3–5 mm) attached to myograph transducers under 1 g tension in organ bath at 37 °C.
Species:  Human
Tissue:  Saphenous vein.
Response measured:  Contraction.
References:  7,12
Physiological Functions
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Heart; central noradrenergic neurons.
References:  14,17
Physiological Consequences of Altering Gene Expression
α2C-adrenoceptor knock-out mice show no change in cardiovascular and sedative effects with a non-selective adrenoceptor agonist.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
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
α2C knockout mice exhibit disruption of presynaptic inhibition of noradrenaline release at low stimulation frequencies.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
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 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
MGI:87936  MP:0008428 abnormal spatial working memory PMID: 10051760  11642653 
Adra2atm1Bkk|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
MGI:87934  MGI:87936  MP:0005447 abnormal synaptic norepinephrine release PMID: 10647009 
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 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
MGI:87936  MP:0002573 behavioral despair PMID: 10523817 
Adra2atm1Bkk|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
MGI:87934  MGI:87936  MP:0001625 cardiac hypertrophy PMID: 10647009 
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 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
MGI:87936  MP:0001488 increased startle reflex PMID: 9526020 
Available Assays
DiscoveRx PathHunter® CHO-K1 ADRA2C β-Arrestin Cell Line (Cat no. 93-0511C2) more info

REFERENCES

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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: α2C-adrenoceptor. Last modified on 27/05/2014. Accessed on 02/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=27.

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