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α2A-adrenoceptor

Previous and Unofficial Names
α2-C10
RG20
Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 450 10q24-q26 ADRA2A 67
Rat 7 450 1 Adra2a 66
Mouse 7 450 19 D2 Adra2a 68
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Receptor Comments
Database Links
ChEMBL Target 52 (Hs), 10655 (Mm), 12744 (Rn)
Ensembl ENSG00000150594 (Hs), ENSMUSG00000033717 (Mm)
Entrez Gene 150 (Hs), 11551 (Mm), 25083 (Rn)
GeneCards ADRA2A (Hs)
HomoloGene 47944 (Hs)
OMIM 104210 (Hs)
PharmGKB Gene PA35 (Hs)
Protein Ontology (PRO) PRO:000001186 (Hs)
RefSeq Nucleotide NM_000681 (Hs), NM_007417 (Mm), NM_012739 (Rn)
RefSeq Protein NP_000672 (Hs), NP_031443 (Mm), NP_036871 (Rn)
UniGene Hs. 249159 (Hs)
UniProt P08913 (Hs), Q01338 (Mm), P22909 (Rn)
Wikipedia α2A-adrenoceptor
Search for 3D structures on the PDB
Search using keywords: Adrenoceptors alpha2A-adrenoceptor Search using accession numbers: P22909 || P08913 || Q01338
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dexmedetomidine Hs Partial agonist 7.6 – 9.6 pKi 90-92
clonidine Hs Partial agonist 7.2 – 9.2 pKi 90-92
oxymetazoline Hs Partial agonist 8.0 pKi 91,93
brimonidine Hs Full agonist 6.7 – 8.7 pKi 90-92
guanfacine Hs Partial agonist 7.3 pKi 91
pergolide Hs Partial agonist 7.3 pKi 1
noradrenaline Hs Full agonist 5.6 – 8.4 pKi 90-92
(±)-adrenaline Hs Full agonist 5.6 – 8.3 pKi 90-91
apomorphine Hs Partial agonist 6.9 pKi 1
xylazine Hs Partial agonist 5.7 pKi 91
Agonist Comments
[3H]UK4,304 binds to the α2A receptor of human platelet membranes with high and low affinity Kd values of 2.6 and 170 nM, respectively with 73% bound at the high affinity site [69]. The discrepancies between the two studies relate to buffer differences (and probably tissue source and membrane preparation methods).
[125I]p-iodoclonidine binds to the human α2A receptor with a Kd of 1.5 nM [70].
The species ortholog of the human α2A receptors (α2D) found in the rat, mouse and cow has significantly different antogonist pharmacology, but the agonist pharmacology appears to be similar.
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 9.5 pKd 71,94
[3H]RX821002 Hs Antagonist 8.8 – 9.5 pKd 71,95
[3H]MK-912 Hs Antagonist 8.9 pKd 93
lisuride Hs Antagonist 10.3 pKi 1
terguride Hs Antagonist 9.5 pKi 1
RX821002 Hs Antagonist 9.2 pKi 93
yohimbine Hs Antagonist 8.4 – 9.2 pKi 93-95
phentolamine Hs Antagonist 8.4 pKi 94-95
rauwolscine Hs Antagonist 8.4 pKi 93
WB 4101 Hs Antagonist 7.6 – 8.9 pKi 93-95
BRL 44408 Hs Antagonist 8.2 pKi 93
bromocriptine Hs Antagonist 8.0 pKi 1
cabergoline Hs Antagonist 7.9 pKi 1
spiroxatrine Hs Antagonist 7.3 pKi 93
piribedil Hs Antagonist 7.1 pKi 1
chlorpromazine Hs Antagonist 5.9 – 6.6 pKi 94-95
ARC-239 Hs Antagonist 5.5 – 6.8 pKi 93-95
prazosin Hs Antagonist 5.3 – 6.5 pKi 93-95
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 [71].
Other agents that have a five-fold or greater lower affinity for the α2D include WB 4101, oxymetazoline, SKF 104078, raubasine and chlorpromazine [70]).
In binding assays, affinities are dependent on buffer condidtions [71].
Allosteric Regulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
HMA Hs Negative 2.5 pKd 96-97
5-(-N-ethyl-N-isopropyl)-amiloride Hs Positive 1.8 pKd 96

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
Phospholipase A2 stimulation
References:  72-74
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  75
Tissue Distribution
Brain > spleen > kidney > aorta = lung = skeletal muscle > heart = liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  82-83
Brain > spleen = kidney = aorta > lung = skeletal muscle.
Absent in heart and liver.
Species:  Rat
Technique:  RNAse protection of mRNA.
References:  84-85
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 cAMP accumulation.
Species:  Human
Tissue:  HT29 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  72
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:  80-81
Physiological Functions
Hypotension.
Species:  Mouse
Tissue:  CNS.
References:  86-87
Sedation.
Species:  Mouse
Tissue:  CNS.
References:  87-89
Analgesia.
Species:  Mouse
Tissue:  Brain.
References:  87-89
Hypothermia.
Species:  Mouse
Tissue:  CNS.
References:  87,89
Anesthetic-sparing effect.
Species:  Mouse
Tissue:  CNS.
References:  87-88
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Vasa deferens, heart.
References:  76-77,87
Physiological Consequences of Altering Gene Expression
The α2A-adrenoceptor knock-out 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:  76
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:  77
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:  78
The hypotensive effects of α2A agonists are abolished in α2A-adrenoceptor knockout mice.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  79
Receptor 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.

To cite this receptor data 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: α2A-adrenoceptor. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=25.


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