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α2C-adrenoceptor

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Target id: 27

Nomenclature: α2C-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 7 462 4p16.3 ADRA2C adrenoceptor alpha 2C 49
Mouse 7 458 5 18.09 cM Adra2c adrenergic receptor, alpha 2c 36
Rat 7 458 14q21 Adra2c adrenoceptor alpha 2C 22
Previous and Unofficial Names Click here for help
α2-C4 | ADRA2L2 | ADRA2RL2 | Adrenergic alpha2C- receptor class I | alpha-2 adrenergic receptor subtype C4 | alpha-2C adrenergic receptor | alpha-2C adrenoreceptor | Adra-2c | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb ada2c_human (Hs), ada2c_mouse (Mm), ada2c_rat (Rn)
Other databases
Alphafold P18825 (Hs), Q01337 (Mm), P22086 (Rn)
ChEMBL Target CHEMBL1916 (Hs), CHEMBL4826 (Mm), CHEMBL314 (Rn)
DrugBank Target P18825 (Hs), P18825 (Hs), P18825 (Hs)
Ensembl Gene ENSG00000184160 (Hs), ENSMUSG00000045318 (Mm), ENSRNOG00000009299 (Rn)
Entrez Gene 152 (Hs), 11553 (Mm), 24175 (Rn)
Human Protein Atlas ENSG00000184160 (Hs)
KEGG Gene hsa:152 (Hs), mmu:11553 (Mm), rno:24175 (Rn)
OMIM 104250 (Hs)
Pharos P18825 (Hs)
RefSeq Nucleotide NM_000683 (Hs), NM_007418 (Mm), NM_138506 (Rn)
RefSeq Protein NP_000674 (Hs), NP_031444 (Mm), NP_612515 (Rn)
UniProtKB P18825 (Hs), Q01337 (Mm), P22086 (Rn)
Wikipedia ADRA2C (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human alpha2C adrenergic G protein-coupled receptor.
PDB Id:  6KUW
Resolution:  2.58Å
Species:  Human
References:  8
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 8.9 pKd 46
⤷ pKd 8.9 [46]
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.4 pKd 48
⤷ pKd 6.4 [48]
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 Agonist 7.0 – 9.3 pKi 28,42,45,48
⤷ pKi 7.0 – 9.3 [28,42,45,48]
apraclonidine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 7.5 pKi 40,48
⤷ pKi 7.5 (Ki 3x10-8 M) [40,48]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pKi 39
⤷ pKi 7.2 [39]
lofexidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pKi 13
⤷ pKi 7.2 (Ki 6.92x10-8 M) [13]
Description: Calculated from [3H]RS-79948-197 radioligand competition binding to membrane preparations from CHO cells expressing human α2C-AR.
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.0 pKi 48
⤷ pKi 7.0 [48]
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.0 – 7.8 pKi 28,42,45,48
⤷ pKi 6.0 – 7.8 [28,42,45,48]
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 Agonist 5.7 – 7.6 pKi 28,38,42,45,48
⤷ pKi 5.7 – 7.6 [28,38,42,45,48]
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.4 – 6.7 pKi 28,32,48,61
⤷ pKi 6.4 – 6.7 [28,32,48,61]
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.4 pKi 48
⤷ pKi 6.4 [48]
(±)-adrenaline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 – 6.2 pKi 28
⤷ pKi 5.8 – 6.2 [28]
guanfacine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 5.4 – 6.2 pKi 28,48
⤷ pKi 5.4 – 6.2 [28,48]
(-)-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 4.5 – 6.8 pKi 28,32,45,48
⤷ pKi 4.5 – 6.8 [28,32,45,48]
(-)-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 4.9 – 5.8 pKi 28,48
⤷ pKi 4.9 – 5.8 [28,48]
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 4.8 – 5.9 pKi 28,48
⤷ pKi 4.8 – 5.9 [28,48]
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 4.8 pKi 48
⤷ pKi 4.8 [48]
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 9.6 pEC50 48
⤷ pEC50 9.6 [48]
Description: ERK1/2 phosphorylation
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.0 pEC50 48
⤷ pEC50 8.0 [48]
Description: ERK1/2 phosphorylation
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.7 pEC50 48
⤷ pEC50 7.7 [48]
Description: ERK1/2 phosphorylation
(-)-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 pEC50 48
⤷ pEC50 7.6 [48]
Description: ERK1/2 phosphorylation
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.1 pEC50 48
⤷ pEC50 7.1 [48]
Description: ERK1/2 phosphorylation
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 5.9 – 8.2 pEC50 32,48
⤷ pEC50 8.2 [48]
Description: ERK1/2 phosphorylation
pEC50 5.9 – 6.9 [32]
Description: 5.88 = value for β-arrestin recruitment and internalization
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.9 pEC50 32
⤷ pEC50 6.9 [32]
Description: β-arrestin recruitment and internalization
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 – 7.7 pEC50 32,48
⤷ pEC50 7.7 [48]
Description: ERK1/2 phosphorylation
pEC50 6.0 – 6.6 [32]
Description: 6.02 = value for β-arrestin recruitment and internalization
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.1 – 8.4 pEC50 32,48
⤷ pEC50 8.4 [48]
Description: ERK1/2 phosphorylation
pEC50 5.1 – 6.6 [32]
Description: 5.14 =value for β-arrestin recruitment and internalization
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 4.6 – 7.8 pEC50 32,48
⤷ pEC50 7.8 [48]
Description: ERK1/2 phosphorylation
pEC50 4.6 – 6.7 [32]
Description: 4.64 =value for β-arrestin recruitment and internalization
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 4.7 – 6.9 pEC50 32,48
⤷ pEC50 6.9 [48]
Description: ERK1/2 phosphorylation
pEC50 4.7 – 5.3 [32]
Description: 4.73 =value for β-arrestin recruitment and internalization
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 9.2 pIC50 48
⤷ pIC50 9.2 [48]
Description: inhibition of cAMP production
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 8.0 – 8.5 pIC50 32,48
⤷ pIC50 8.0 – 8.5 [32,48]
Description: inhibition of cAMP production
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.4 – 8.2 pIC50 32,48
⤷ pIC50 7.4 – 8.2 [32,48]
Description: inhibition of cAMP production
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.5 – 7.7 pIC50 32,48
⤷ pIC50 7.5 – 7.7 [32,48]
Description: inhibition of cAMP production
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.5 – 8.6 pIC50 32,48
⤷ pIC50 6.5 – 8.6 [32,48]
Description: inhibition of cAMP production
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pIC50 48
⤷ pIC50 7.2 [48]
Description: inhibition of cAMP production
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.2 pIC50 48
⤷ pIC50 7.2 [48]
Description: inhibition of cAMP production
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.1 pIC50 48
⤷ pIC50 7.1 [48]
Description: inhibition of cAMP production
guanabenz Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.0 – 7.9 pIC50 2,32,48
⤷ pIC50 6.0 – 7.9 (IC50 1.106x10-6 M) [2,32,48]
Description: inhibition of cAMP production
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pIC50 48
⤷ pIC50 6.8 [48]
Description: inhibition of cAMP production
(-)-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 6.7 pIC50 48
⤷ pIC50 6.7 [48]
Description: inhibition of cAMP production
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.3 – 6.6 pIC50 32,48
⤷ pIC50 6.3 – 6.6 [32,48]
Description: inhibition of cAMP production
Agonist Comments
[125I]p-iodoclonidine binds to the human α2C receptor with a pKd of 8.9 [46]. 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. Guanabenz order of affinity is α2A-AR>α2B-AR>α2C-AR [2]. There are currently no selective α2C-AR selective agonists available. Clinical uses: Clonidine is used to treat high blood pressure, guanfacine for ADHD and tizanidine to relieve muscle spasticity. Apraclonidine [40] 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 α2A-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
ORM-10921 Small molecule or natural product Hs Antagonist 9.8 pKB 52
⤷ pKB 9.8 [52]
JP1302 Small molecule or natural product Hs Antagonist 6.9 – 7.8 pKB 47,53
⤷ pKB 6.9 – 7.8 [47,53]
[3H]MK-912 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.1 pKd 61
⤷ pKd 10.1 (Kd 8.6x10-11 M) [61]
[3H]rauwolscine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.1 – 9.9 pKd 6,11,47
⤷ pKd 9.1 – 9.9 [6,11,47]
[3H]RX821002 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.2 – 9.2 pKd 11-12,47
⤷ pKd 8.2 – 9.2 [11-12,47]
ORM-12741 Small molecule or natural product Hs Antagonist 10.1 – 11.0 pKi 56
⤷ pKi 10.1 – 11.0 [56]
MK-912 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.8 – 10.0 pKi 47
⤷ pKi 9.8 – 10.0 [47]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.3 – 9.9 pKi 38-39,47
⤷ pKi 9.3 – 9.9 [38-39,47]
RS79948 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.4 pKi 47
⤷ pKi 9.4 [47]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.1 pKi 39
⤷ pKi 9.1 [39]
rauwolscine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 pKi 61
⤷ pKi 9.1 [61]
yohimbine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.5 – 9.5 pKi 6,12,47,61
⤷ pKi 8.5 – 9.5 [6,12,47,61]
ORM-10921 Small molecule or natural product Hs Antagonist 8.9 pKi 52
⤷ pKi 8.9 [52]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.7 – 9.0 pKi 47,61
⤷ pKi 8.7 – 9.0 [47,61]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 pKi 39
⤷ pKi 8.8 [39]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 9.4 pKi 6,12,47,61
⤷ pKi 8.2 – 9.4 [6,12,47,61]
atipamezole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 47
⤷ pKi 8.5 [47]
RX821002 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 – 8.7 pKi 47,61
⤷ pKi 8.1 – 8.7 [47,61]
EGIS-11150 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 pKi 23
⤷ pKi 7.9 (Ki 1.3x10-8 M) [23]
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.6 – 7.9 pKi 6,12,47
⤷ pKi 7.6 – 7.9 [6,12,47]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.7 pKi 39
⤷ pKi 7.7 [39]
all-trans-4-oxo-retinoic acid Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.7 pKi 21
⤷ pKi 7.7 [21]
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.3 – 8.0 pKi 27,47
⤷ pKi 7.3 – 8.0 [27,47]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.6 pKi 39,48
⤷ pKi 7.6 [39,48]
ARC-239 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 8.4 pKi 6,12,47,61
⤷ pKi 6.7 – 8.4 [6,12,47,61]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pKi 39
⤷ pKi 7.4 [39]
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.0 – 7.7 pKi 21,47
⤷ pKi 7.0 – 7.7 [21,47]
Description: Inhibition of [3H]rauwolscine binding.
prazosin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 – 8.0 pKi 6,12,47,61
⤷ pKi 6.5 – 8.0 [6,12,47,61]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 pKi 39
⤷ pKi 7.2 [39]
idazoxan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 pKi 47
⤷ pKi 7.2 [47]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.9 – 7.4 pKi 6,12,47
⤷ pKi 5.9 – 7.4 [6,12,47]
BRL 44408 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 – 6.8 pKi 47,61
⤷ pKi 6.2 – 6.8 [47,61]
tolazoline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 5.4 pKi 28
⤷ pKi 5.4 (Ki 3.715x10-6 M) [28]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
MK-912 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 9.6 pIC50 32
⤷ pIC50 8.2 – 9.6 [32]
yohimbine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.5 – 8.2 pIC50 32
⤷ pIC50 6.5 – 8.2 [32]
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 30
⤷ pIC50 6.7 (IC50 1.995x10-7 M) [30]
[11C]-ORM-13070 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist - - 1,33,56
⤷ [1,33,56]
Antagonist Comments
Mirtazapine is an antagonist of α2-adrenoceptors and serotonin 5-HT2A and 5-HT2C receptors. JP1302 displays some α2C-AR selectivity as does MK912 that has very high affinity for α2C-AR. Highly selective and potent α2C-AR antagonists are emerging- ORM-10921 and ORM-12741 (10-100 fold selective vs. α1A- and α1B-AR) - that cross the BBB and have potential utility for treatment of cognitive dysfunction and neuropsychiatric symptoms. Rauwolscine is a stereoisomer of yohimbine. Bromocriptine can act as a partial agonist in some α2-AR assay systems. Clinical uses: Atipamezole is an α2-AR antagonist used in veterinary medicine to reverse the effects of dexmedetomidine.
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:  7,35,48
Tissue Distribution Click here for help
Brain = kidney > aorta = lung = skeletal muscle = heart = spleen.
Absent in the liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  15,43
Brain >> kidney.
Absent in spleen, aorta, heart, liver, lung, skeletal muscle.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  5,25
Striatum, caudate nucleus and putamen.
Species:  Human
Technique:  5-30 min post injection of [11C]ORM13070 – in vivo PET/CT scanning.
References:  33-34
α2C-AR in human striatum.
Species:  Human
Technique:  Autoradiography.
References:  18
Adrenal glands>small intestine>brain>liver>pancreas>salivary gland>thymus – high binding in striatum/olfactory tubercle.
Species:  Rat
Technique:  5 min post injection of [11C]ORM13070 – in vivo PET/CT scanning.
References:  1
α2C-AR mRNA labeling primarily in the olfactory bulb, cerebral cortex, islands of Calleja, striatum, hippocampal formation, cerebellar cortex, and dorsal root ganglia.
Species:  Rat
Technique:  In situ hybridisation.
References:  41,55
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
Measurment of adenylate cyclase activity in intact cell preparations (either native or transfected) -inhibition of cAMP accumulation.
Species:  Human
Tissue:  HT29 and COS cells expressing human α2-AR subtypes.
Response measured:  Inhibition of cAMP accumulation after [3H]adenine prelabeling.
References:  7
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:  14,24
Inhibition of adenylate cyclase activity in CHO-K1 cells expressing human α2C-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Inhibition of cAMP accumulation induced by forskolin.
References:  32
Cytosolic free Ca2+ concentration in CHO-K1 cells expressing human α2C-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Fluorometric measurement of cytoplasmic Ca2+ concentration in cells co-expressing α2C-AR and Gαqi5.
References:  32
β-arrestin recruitment in CHO-K1 cells expressing human α2C-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Pathhunter® β-arrestin recruitment assay.
References:  32
Receptor internalisation in CHO-K1 cells expressing human α2C-adrenoceptors.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2C-AR.
Response measured:  Whole cell [3H]rauwolscine binding, CRE-SPAP gene transcription, [3H]cAMP accumulation, ERK1/2 phosphorylation.
References:  32
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 α2C-AR.
Response measured:  Whole cell [3H]rauwolscine binding, CRE-SPAP gene transcription, [3H]cAMP accumulation, ERK1/2 phosphorylation.
References:  48
The signalling 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.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2C-AR.
Response measured:  Whole cell [3H]rauwolscine binding.
References:  47
Constitutive dimer formation between AT1 receptor and α2CAR and atypical Gs-PKA signalling.
Species:  Human
Tissue:  HEK293-T cells.
Response measured:  BRET between AT1-R Rluc8/α2C-AR Rluc8 and CD8GFP2 – hetrodimers show atypical Gs-PKA signalling.
References:  4
Multiplexed dynamic mass redistribution/HTRF-based cAMP detection assay.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  HTRF detection of cAMP inhibition and change in label free DMR index.
References:  31
Kinetic measurement of off rate constants for α2C-AR ligands.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Measurement of kinetic off rate of unlabelled ligands using a novel radioligand binding technique.
References:  60
Physiological Functions Click here for help
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Heart; central noradrenergic neurons.
References:  26,29
Formation of functional heterodimers between α2C-A and AT1-R.
Species:  Human
Tissue:  HEK293 cells expressing human receptors. Heterodimers may have a function in hypertension and heart failure.
References:  4
Suppression of L type Ca2+ current in cardiac myocytes.
Species:  Mouse
Tissue:  Cardiac myocytes. Patch clamp studies examining α2C-AR mediated inhibition of L-type Ca2+ current.
References:  17
Locomotor activity and hand-eye coordination.
Species:  Monkey
Tissue:  α2C-AR antagonist treatment improves locomotor activity and hand-eye coordination in model of Parkinson’s disease.
References:  44
Antidepressant, antipsychotic and cognitive deficit effects. (rat AND mouse)
Species:  Rat
Tissue:  Forced swimming and prepulse inhibition behavioural models. PCP induced cognitive deficits.
References:  52,54,62-63
Cytokine upregulation in kidney.
Species:  Rat
Tissue:  Kidney damage due to ischaemia/reperfusion reduced by α2C-AR antagonist.
References:  57,59
Down regulation of α2C-AR with age.
Species:  Mouse
Tissue:  Sympathetic induced vasoconstriction.
References:  58
Venous vasoconstriction.
Species:  Human
Tissue:  Veins.
References:  16
Exaggerated cold induced vasoconstriction.
Species:  Human
Tissue:  Skin blood vessels.
References:  20
Physiological Consequences of Altering Gene Expression Click here for help
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:  29
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:  37
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:  26
Knockdown of α2C-AR in occipital cortex rescues LTP in prenatally malnourished rats.
Species:  Rat
Tissue:  Occipital cortex.
Technique:  Antisense oligodeoxynucleotide (ODN) of α2C-AR mRNA administered to occipital cortex rescues impaired LTP and visuospatial memory associated with α2C-AR overexpression following prenatal malnutrition.
References:  3
Endothelial dysfunction in mouse small arteries.
Species:  Mouse
Tissue:  Aortic and mesenteric small arteries.
Technique:  α2A- /α2C-AR double knockout mice.
References:  9
α2C-AR required for bone loss due to thyrotoxicosis.
Species:  Mouse
Tissue:  Bone.
Technique:  α2C-AR knockout mice.
References:  10
α2C-AR expression and function increased by oestrogens.
Species:  Human
Tissue:  Vascular smooth muscle cells from cutaneous arterioles.
Technique:  Oestrogen treatment upregulated α2C-AR expression and function by an EPAC-mediated JNK/AP-1 dependent mechanism.
References:  19
α2C-AR knockout mice exhibit accelerated wound healing.
Species:  Mouse
Tissue:  Myofibroblasts, neutrophils, macrophages.
Technique:  α2C-AR knockout mice, blood vessel formation, myofibroblast differentiation, cell migration, actin expression and collagen deposition.
References:  51
Reduced vasoconstriction with ageing.
Species:  Mouse
Tissue:  Down regulation of α2C-AR with ageing associated with reduced sympathetic vasoconstriction.
Technique:  Blood vessels.
References:  58
2C-AR polymorphism associated with opiate abuse and dependence.
Species:  Human
Tissue:  Brain.
Technique:  DNA extraction and genotyping. Association between α2C-del322-325-AR and opiate abuse and dependence.
References:  50
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
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 
Biologically Significant Variants Click here for help
Type:  Polymorphism
Species:  Human
Description:  α2C-del322-325-AR (loss-of-function phenotype) is associated with opiate abuse and dependence.
References:  50

References

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