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α2A-adrenoceptor

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Target not currently curated in GtoImmuPdb

Target id: 25

Nomenclature: α2A-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 7 465 10q25.2 ADRA2A adrenoceptor alpha 2A 38
Mouse 7 465 19 49.04 cM Adra2a adrenergic receptor, alpha 2a 44
Rat 7 465 1q55 Adra2a adrenoceptor alpha 2A 40
Previous and Unofficial Names Click here for help
α2D | ADRA2 | ADRA2R | Adrenergic alpha 2A receptor | Adra-2 | Adra-2a | alpha2A | alpha2A-adrenergic receptor | alpha2A-AR | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb ada2a_human (Hs), ada2a_mouse (Mm), ada2a_rat (Rn)
Other databases
Alphafold P08913 (Hs), Q01338 (Mm), P22909 (Rn)
ChEMBL Target CHEMBL1867 (Hs), CHEMBL4075 (Mm), CHEMBL327 (Rn)
DrugBank Target P08913 (Hs), P08913 (Hs), P08913 (Hs)
Ensembl Gene ENSG00000150594 (Hs), ENSMUSG00000033717 (Mm), ENSRNOG00000047545 (Rn)
Entrez Gene 150 (Hs), 11551 (Mm), 25083 (Rn)
Human Protein Atlas ENSG00000150594 (Hs)
KEGG Gene hsa:150 (Hs), mmu:11551 (Mm), rno:25083 (Rn)
OMIM 104210 (Hs)
Pharos P08913 (Hs)
RefSeq Nucleotide NM_000681 (Hs), NM_007417 (Mm), NM_012739 (Rn)
RefSeq Protein NP_000672 (Hs), NP_031443 (Mm), NP_036871 (Rn)
UniProtKB P08913 (Hs), Q01338 (Mm), P22909 (Rn)
Wikipedia ADRA2A (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structures of the alpha2A adrenergic receptor in complex with an antagonist RSC.
PDB Id:  6KUX
Ligand:  RS79948
Resolution:  2.7Å
Species:  Human
References:  11
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
[3H]brimonidine (UK14304) Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Agonist 9.1 pKd 53
⤷ pKd 9.1 [53]
[3H]clonidine Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Partial agonist 8.8 pKd 70
⤷ pKd 8.8 [70]
[125I]p-iodoclonidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Partial agonist 8.8 pKd 60
⤷ pKd 8.8 [60]
[3H]clonidine Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Partial agonist 7.6 pKd 68
⤷ pKd 7.6 [68]
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 Partial agonist 7.6 – 9.6 pKi 33,45,57,59,62
⤷ pKi 7.6 – 9.6 [33,45,57,59,62]
apraclonidine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 8.5 pKi 52
⤷ pKi 8.5 (Ki 2.9x10-9 M) [52]
lofexidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.4 pKi 15
⤷ pKi 8.4 (Ki 4.36x10-9 M) [15]
Description: Calculated from [3H]RS-79948-197 radioligand competition binding to membrane preparations from CHO cells expressing human α2A-AR.
oxymetazoline 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 7.3 – 8.6 pKi 33,45,62,73
⤷ pKi 7.3 – 8.6 [33,45,62,73]
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 Agonist 6.7 – 9.2 pKi 33,57,59,62
⤷ pKi 6.7 – 9.2 [33,57,59,62]
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.6 pKi 62
⤷ pKi 7.6 [62]
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 Full agonist 6.4 – 8.7 pKi 33,45,57,59,62
⤷ pKi 6.4 – 8.7 [33,45,57,59,62]
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.0 – 7.7 pKi 33,62
⤷ pKi 7.0 – 7.7 [33,62]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.3 pKi 49
⤷ pKi 7.3 [49]
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.0 pKi 62
⤷ pKi 7.0 [62]
guanfacine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 6.6 – 7.3 pKi 33,46,62
⤷ pKi 6.6 – 7.3 [33,46,62]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 6.9 pKi 49
⤷ pKi 6.9 [49]
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.0 pKi 62
⤷ pKi 6.0 [62]
(-)-adrenaline 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 Immunopharmacology Ligand Hs Full agonist 3.7 – 7.4 pKi 33,59,62
⤷ pKi 3.7 – 7.4 [33,59,62]
(-)-noradrenaline 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 Hs Full agonist 3.6 – 7.4 pKi 33,59,62
⤷ pKi 3.6 – 7.4 [33,59,62]
xylazine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 4.9 – 5.7 pKi 33,62
⤷ pKi 4.9 – 5.7 [33,62]
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.0 pKi 62
⤷ pKi 5.0 [62]
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 9.1 pEC50 62
⤷ pEC50 9.1 [62]
Description: increased ERK1/2 phosphorylation
guanabenz Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.3 – 9.1 pEC50 33,62
⤷ pEC50 9.1 [62]
Description: increased ERK1/2 phosphorylation
pEC50 8.3 [33]
Description: GTPγs binding
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.6 – 9.5 pEC50 33,62
⤷ pEC50 9.5 [62]
Description: increased ERK1/2 phosphorylation
pEC50 8.5 [33]
pEC50 7.6 [62]
Description: increased cAMP generation
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.5 – 9.0 pEC50 33,62
⤷ pEC50 9.0 [62]
Description: increased ERK1/2 phosphorylation
pEC50 7.3 [33]
Description: GTPγs binding
pEC50 6.5 [62]
Description: increased cAMP generation
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.4 – 9.0 pEC50 33,62
⤷ pEC50 9.0 [62]
Description: increased ERK1/2 phosphorylation
pEC50 7.6 [33]
Description: GTPγs binding
pEC50 6.4 [62]
Description: increased cAMP generation
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.8 – 8.5 pEC50 62
⤷ pEC50 8.5 [62]
Description: increased ERK1/2 phosphorylation
pEC50 5.8 [62]
Description: increased cAMP generation
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.1 pEC50 62
⤷ pEC50 7.1 [62]
Description: increased cAMP generation
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 5.8 – 8.4 pEC50 62
⤷ pEC50 8.4 [62]
Description: increased ERK1/2 phosphorylation
pEC50 5.8 [62]
Description: increased cAMP generation
(-)-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 5.5 – 8.0 pEC50 33,62
⤷ pEC50 8.0 [62]
Description: increased ERK1/2 phosphorylation
pEC50 6.8 [33]
Description: GTPγs binding
pEC50 5.5 [62]
Description: increased cAMP generation
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.3 – 7.7 pEC50 33,62
⤷ pEC50 7.7 [62]
Description: increased ERK1/2 phosphorylation
pEC50 6.7 [33]
Description: GTPγs binding
pEC50 5.3 [62]
Description: increased cAMP generation
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.1 – 7.5 pEC50 33,62
⤷ pEC50 7.5 [62]
Description: increased ERK1/2 phosphorylation
pEC50 5.7 [33]
Description: GTPγs binding
pEC50 5.1 [62]
Description: increased cAMP generation
dexmedetomidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 9.3 pIC50 62
⤷ pIC50 9.3 [62]
Description: inhibition of forskolin stimulated cAMP generation
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 8.9 pIC50 62
⤷ pIC50 8.9 [62]
Description: inhibition of forskolin stimulated cAMP generation
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.4 pIC50 62
⤷ pIC50 8.4 [62]
Description: inhibition of forskolin stimulated cAMP generation
clonidine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 8.2 pIC50 62
⤷ pIC50 8.2 [62]
Description: inhibition of forskolin stimulated cAMP generation
xylometazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 8.1 pIC50 62
⤷ pIC50 8.1 [62]
Description: inhibition of forskolin stimulated cAMP generation
guanfacine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.0 pIC50 62
⤷ pIC50 8.0 [62]
Description: inhibition of forskolin stimulated cAMP generation
guanabenz Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 7.4 – 8.4 pIC50 4,62
⤷ pIC50 7.4 – 8.4 [4,62]
Description: inhibition of forskolin stimulated cAMP generation
pIC50 7.4 (IC50 4.1x10-8 M) [4,62]
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.8 pIC50 62
⤷ pIC50 7.8 [62]
Description: inhibition of forskolin stimulated cAMP generation
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.6 pIC50 62
⤷ pIC50 7.6 [62]
Description: inhibition of forskolin stimulated cAMP generation
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 7.5 pIC50 62
⤷ pIC50 7.5 [62]
Description: inhibition of forskolin stimulated cAMP generation
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.6 pIC50 62
⤷ pIC50 6.6 [62]
Description: inhibition of forskolin stimulated cAMP generation
(-)-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 6.5 pIC50 62
⤷ pIC50 6.5 [62]
Description: inhibition of forskolin stimulated cAMP generation
xylazine Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.5 pIC50 62
⤷ pIC50 6.5 [62]
Description: inhibition of forskolin stimulated cAMP generation
View species-specific agonist tables
Agonist Comments
[3H]UK4,304 binds to the α2A receptor of human platelet membranes with high affinity (pKd 9.1) [53]. [125I]p-iodoclonidine binds to the human α2A receptor with a pKd of 8.8 [60]. The species ortholog of the human α2A ARs (α2D) found in the rat, mouse and cow has significantly different antagonist pharmacology, but the agonist pharmacology appears to be similar. Many of the compounds listed as agonists will behave as full or partial agonists depending on the system in which they are studied and will tend towards full agonism in recombinant systems with high receptor expression. Moxonidine is marketed as a selective imidazoline I1 receptor agonist but also has significant activity at α2-AR. Clonidine is used to treat high blood pressure, guanfacine for ADHD and tizanidine to relieve muscle spasticity. Apraclonidine [52] and bromonidine are used in eye drops to relieve glaucoma. A number of anti-Parkinsonian drugs such as lisuride, roxindole and terguride have high potency competing for α2-AR binding [49]. 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. Although the α2-AR antagonist atipamezole is widely used to reverse the effects of xylazine in veterinary medicine this role has yet to be established in the clinic. The approved drug oxymetazoline has been mapped to the primary targets α1A and α2A ARs as these have comparably the highest affinity interaction with the drug. This does not preclude clinically relevant activity at other adrenoceptors. Guanabenz order of affinity is α2A-AR>α2B-AR>α2C-AR [4].
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 8.6 – 9.5 pKd 7,13,61
⤷ pKd 8.6 – 9.5 [7,13,61]
[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 73
⤷ pKd 8.9 (Kd 1.25x10-9 M) [73]
[3H]RX821002 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.3 – 9.5 pKd 13-14,61
⤷ pKd 8.3 – 9.5 [13-14,61]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.0 – 10.3 pKi 49,61
⤷ pKi 9.0 – 10.3 [49,61]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.5 pKi 49
⤷ pKi 9.5 [49]
RS79948 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 pKi 61
⤷ pKi 8.9 [61]
yohimbine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.4 – 9.2 pKi 7,14,61,73
⤷ pKi 8.4 – 9.2 [7,14,61,73]
MK-912 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.7 pKi 61
⤷ pKi 8.7 [61]
RX821002 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 – 9.2 pKi 61,73
⤷ pKi 8.1 – 9.2 [61,73]
atipamezole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 61
⤷ pKi 8.5 [61]
rauwolscine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 73
⤷ pKi 8.4 [73]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist 8.3 pKi 9
⤷ pKi 8.3 (Ki 5x10-9 M) [9]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 – 8.9 pKi 7,14,61
⤷ pKi 7.6 – 8.9 [7,14,61]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 – 8.3 pKi 49,62
⤷ pKi 8.0 – 8.3 [49,62]
BRL 44408 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 – 8.8 pKi 61,73,76
⤷ pKi 7.2 – 8.8 [61,73,76]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 pKi 49
⤷ pKi 7.9 [49]
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.3 – 8.4 pKi 7,14,61
⤷ pKi 7.3 – 8.4 [7,14,61]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.3 pKi 61
⤷ pKi 7.3 [61]
idazoxan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 pKi 61
⤷ pKi 7.2 [61]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 – 7.3 pKi 61,73
⤷ pKi 7.0 – 7.3 [61,73]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 49
⤷ pKi 7.1 [49]
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.7 – 7.4 pKi 29,61
⤷ pKi 6.7 – 7.4 [29,61]
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.8 – 7.1 pKi 21,61
⤷ pKi 6.8 – 7.1 [21,61]
Description: Inhibition of [3H]rauwolscine binding.
tolazoline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.7 pKi 33
⤷ pKi 6.7 (Ki 1.99x10-7 M) [33]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
ARC-239 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 – 6.8 pKi 7,14,61
⤷ pKi 5.5 – 6.8 [7,14,61]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.5 – 6.6 pKi 7,14,61
⤷ pKi 5.5 – 6.6 [7,14,61]
prazosin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.3 – 6.5 pKi 7,14,61
⤷ pKi 5.3 – 6.5 [7,14,61]
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 4.8 pKi 9
⤷ pKi 4.8 (Ki 1.4x10-5 M) [9]
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.1 pIC50 36
⤷ pIC50 7.1 (IC50 8.511x10-8 M) [36]
Antagonist Comments
The species orthologs of the human α2A receptors (α2D) found in the rat, mouse, cow and chicken have significantly different antagonist pharmacology.
For example, [3H]rauwolscine has a much lower affinity for the α2D as compared to the α2A, whereas [3H]RX821002 has higher affinity [13]. Rauwolscine is a stereoisomer of yohimbine. Other agents that have a five-fold or greater lower affinity for the α2D include WB4101, oxymetazoline, SKF104078, raubasine, chlorpromazine [55]) and BRL44408 [31]. BRL44408 displays some selectivity for α2A-AR and MK912 for the α2C-AR [61]. Bromocriptine can act as a partial agonist in some α2-AR assay systems. Many antidepressants and antipsychotics have significant activity at α2-AR subtypes [61]. In binding assays, affinities are influenced by buffer conditions [13].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
5-(N,N-hexamethylene)-amiloride Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Negative 2.5 pKd 41,75
⤷ pKd 2.5 [41,75]
ethylisopropylamiloride Small molecule or natural product Click here for species-specific activity table Hs Positive 1.8 pKd 75
⤷ pKd 1.8 [75]
C10 (homobivalent 4-aminoquinoline) Small molecule or natural product Hs Positive 7.5 pKi 42
⤷ pKi 7.5 [42]
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Potassium channel
Calcium channel
Phospholipase A2 stimulation
Comments:  Inhibition of voltage dependent Ca2+ channels
Augmentation of inwardly rectifying K+ channels.
References:  8,34,43,62,67
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Comments:  The physiological significance of this mechanism is unknown. Although this seems to be a contradiction of the primary transduction mechanism, some α2-AR agonists activate adenylyl cyclase at concentrations higher than those that inhibit adenylyl cyclase - hence biphasic responses can be observed.
References:  17,62,67
Tissue Distribution Click here for help
Brain > spleen > kidney > aorta = lung = skeletal muscle > heart = liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  18,58
Brain: mainly postsynaptic in prefrontal cortex.
Species:  Human
Technique:  Subcellular fractionation and Western blot.
References:  19
Inferior colliculus.
Species:  Mouse
Technique:  In situ hybridisation.
References:  74
Brain > spleen = kidney = aorta > lung = skeletal muscle.
Absent in heart and liver.
Species:  Rat
Technique:  RNAse protection of mRNA.
References:  6,22
Localization of α2A-AR in rat central nervous system.
Species:  Rat
Technique:  Immunohistochemistry.
References:  63,72
α2A-AR mRNA labeling in cerebral cortex, hypothalamic paraventricular nucleus, reticular thalamic nucleus, pontine nuclei, locus coeruleus, vestibular nuclei, trapezoid nuclei, deep cerebellar nuclei, nucleus tractus solitarii, ventrolateral medullary reticular formation, and intermediolateral cell column of thoracic spinal cord.
Species:  Rat
Technique:  In situ hybridisation.
References:  54,66
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 cAMP accumulation.
Species:  Human
Tissue:  HT29 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  8
Inhibition of adenylate cyclase.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Optimised FRET based Epac biosensors.
References:  69
The signalling and selectivity of α-AR agonists for the human α2A, α2B and α2C-ARs and comparison with human α1 and β-ARs.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2A-AR.
Response measured:  Whole cell [3H]rauwolscine binding, CRE-SPAP gene transcription, [3H]cAMP accumulation, ERK1/2 phosphorylation.
References:  62
The affinity and selectivity of α-AR antagonists, antidepressants and antipsychotics for the human α2A-, α2B-, and α2C-ARs and comparison with human α1- and β-ARs.
Species:  Human
Tissue:  CHO-K1 cell stably expressing α2A-AR .
Response measured:  Whole cell [3H]rauwolscine binding.
References:  61
Segments of saphenous vein are incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing uptake 1 and uptake 2 blockers. The antagonists potencies in facilitating the electrically (2 Hz) evoked tritium overflow is determined.
Species:  Human
Tissue:  Saphenous vein.
Response measured:  Electrically evoked tritium overflow.
References:  16,51
Heterodimer formation between α2A-adrenoceptors and μ opioid receptors.
Species:  Rat
Tissue:  NTS neurons.
Response measured:  Immunofluorescence, co-immunoprecipitation, proximity ligation assays.
References:  71
Physiological Functions Click here for help
Hypotension.
Species:  Mouse
Tissue:  CNS.
References:  35,47
Sedation.
Species:  Mouse
Tissue:  CNS.
References:  27,35,39
Hypothermia.
Species:  Mouse
Tissue:  CNS.
References:  27,35
Anesthetic-sparing effect.
Species:  Mouse
Tissue:  CNS.
References:  35,39
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Vasa deferens, heart.
References:  2,23,35
Analgesia and sedation.
Species:  Mouse
Tissue:  Brain.
References:  27,35,37,39
Attenuation of insulin release.
Species:  Mouse
Tissue:  Pancreatic islets.
References:  30
Inflammation.
Species:  Mouse
Tissue:  Cytokines in blood, hippocampus.
References:  48
Gut inflammation.
Species:  Mouse
Tissue:  Colon – inflammation enhanced by α2-adrenoceptor agonists and reduced by α2A-selective antagonist.
References:  77
Basal ganglia transmission and motor function.
Species:  Rat
Tissue:  Locus coeruleus α2A-adrenoceptor levels decreased in 6-OHDA lesioned rats restored by L-DOPA treatment.
References:  1
Prefontal cortex cognitive disorders.
Species:  Human
Tissue:  Prefrontal cortex.
References:  3
Protective role of prejunctional α2A-adrenoceptors in hypertensive kidney disease.
Species:  Mouse
Tissue:  Kidney, blood pressure.
References:  25
Bone turnover and osteoporosis.
Species:  Human
Tissue:  Bone samples and osteosarcoma HOS cells.
References:  50
Central cardiovascular regulation – hypotension and bradycardia.
Species:  Human
Tissue:  CNS.
References:  64
Sedation and analgesia.
Species:  Human
Tissue:  CNS.
References:  64
nhibition of insulin release from the pancreas.
Species:  Human
Tissue:  Pancreas.
References:  64
Suppression of opiate withdrawal.
Species:  Human
Tissue:  CNS.
References:  26
Skeletal muscle relaxation.
Species:  Human
Tissue:  Skeletal muscle.
References:  5,20,28
Lowering of intraocular pressure.
Species:  Human
Tissue:  Eye.
References:  32
Inhibition of neurotransmitter release.
N.B. in mammals, including humans.
Species:  Human
Tissue:  CNS and peripheral nervous system.
References:  64
Physiological Consequences of Altering Gene Expression Click here for help
α2A-adrenoceptor knockout mice exhibit disruption of presynaptic inhibition of noradrenaline release at high stimulation frequencies. This study showed that the α2A receptor is the principal autoreceptor in the presynaptic feedback loop regulating noradrenaline release. However, another α2 autoreceptor is also present.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  23
The hypotensive effects of α2A agonists are abolished in α2A-adrenoceptor knockout mice.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  24
α2A-adrenoceptor knockout mice exhibit no amitriptyline-induced (a tricyclic antidepressant) or clonidine-induced analgesia. This study shows that the α2A-adrenoceptors are involved in the sedative effects of these drugs.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  56
Blockade of α2A-adrenoceptors may be exploited to reduce visceral fat and to improve insulin secretion.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  65
Prejunctional inhibitory α2A-adrenoceptors have a protective role in pathophysiologic conditions with an activated renin-angiotensin system, such as hypertensive kidney disease, and support the concept of sympatholytic therapy as a treatment.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  25
α2A-adrenoceptor knockout mice show an increase in sympathetic activity, resting tachycardia, depletion of cardiac tissue noradrenaline concentration and down-regulation of cardiac β-adrenoceptors.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  2
α2A-adrenoceptor deficiency ameliorates lung injury by increasing noradrenaline concentrations in lung and inhibiting activation of alveolar macrophages.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  12
α2A-ARs have both positive and negative modulatory effects on opioid antinociception.
Species:  Mouse
Tissue:  Spinal cord.
Technique:  Transgenesis.
References:  10
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 Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87934  MP:0002078 abnormal glucose homeostasis PMID: 17992256 
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 
Adra2atm1Bkk Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:87934  MP:0005447 abnormal synaptic norepinephrine release PMID: 10647009 
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 Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:87934  MP:0000230 abnormal systemic arterial blood pressure PMID: 10385696 
Adra2atm1Lel Adra2atm1Lel/Adra2atm1Lel
involves: 129S2/SvPas * C57BL/6		 MGI:87934  MP:0000230 abnormal systemic arterial blood pressure PMID: 8670421 
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|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 
Adra2atm1Bkk Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87934  MP:0000189 hypoglycemia PMID: 17992256 
Adra2atm1Bkk Adra2atm1Bkk/Adra2atm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:87934  MP:0002626 increased heart rate PMID: 10385696 
Adra2atm1Qiwa Adra2atm1Qiwa/Adra2atm1Qiwa
B6.129-Adra2a		 MGI:87934  MP:0002169 no abnormal phenotype detected PMID: 19276088 
General Comments
Receptors designated as α2A and α2D are species orthologues. Although these receptors are highly homologous, they have sufficiently different pharmacology to have been designated as separate subtypes in the literature. The α2A subtype is found in the human, pig and rabbit, whereas the α2D is found in the rat, mouse and cow.

References

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