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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 23
Mouse 7 465 19 49.04 cM Adra2a adrenergic receptor, alpha 2a 28
Rat 7 465 1q55 Adra2a adrenoceptor alpha 2A 25
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)
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline
Comments: Adrenaline exhibits greater relative potency than 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
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 19,29,38,40,42
⤷ pKi 7.6 – 9.6 [19,29,38,40,42]
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 34
⤷ pKi 8.5 (Ki 2.9x10-9 M) [34]
lofexidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 8.4 pKi 9
⤷ pKi 8.4 (Ki 4.36x10-9 M) [9]
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 8.0 – 8.6 pKi 19,29,42-43
⤷ pKi 8.0 – 8.6 (Ki 1x10-8 – 2.8x10-9 M) [19,29,42-43]
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 Partial agonist 7.2 – 9.2 pKi 19,38,40,42
⤷ pKi 7.2 – 9.2 [19,38,40,42]
brimonidine 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 6.7 – 8.7 pKi 19,29,38,40,42
⤷ pKi 6.7 – 8.7 [19,29,38,40,42]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.3 pKi 32
⤷ pKi 7.3 [32]
guanfacine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 7.1 – 7.3 pKi 19,30,42
⤷ pKi 7.1 – 7.3 [19,30,42]
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 32
⤷ pKi 6.9 [32]
(-)-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 5.8 – 7.4 pKi 19,40,42
⤷ pKi 5.8 – 7.4 [19,40,42]
(-)-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 5.6 – 7.4 pKi 19,40,42
⤷ pKi 5.6 – 7.4 [19,40,42]
xylazine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.7 pKi 19
⤷ pKi 5.7 [19]
guanabenz Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 7.4 pIC50 2,42
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [2,42]
tizanidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist - - 42
⤷ [42]
moxonidine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist - - 42
⤷ [42]
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 [35]. 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 [36].
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.

Apraclonidine is an approved drug agonist of α2-adrenoceptors [34].
The approved drug oxymetazoline has been mapped to the primary targets α1A and α2A adrenoceptors as these have comparably the highest affinity interaction with the drug. This does not preclude clinically relevant activity at other adrenoceptors.
As the endogenous ligand, (-)-adrenaline has intrinsic activity across the adrenoceptor family, but we've only tagged α1D and α2A 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 [2].
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 9.5 pKd 4,7
⤷ pKd 9.5 [4,7]
[3H]RX821002 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.8 – 9.5 pKd 7-8
⤷ pKd 8.8 – 9.5 [7-8]
[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 43
⤷ pKd 8.9 (Kd 1.25x10-9 M) [43]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 10.3 pKi 32
⤷ pKi 10.3 [32]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.5 pKi 32
⤷ pKi 9.5 [32]
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 4,8,41,43
⤷ pKi 8.4 – 9.2 [4,8,41,43]
RX821002 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 – 9.2 pKi 41,43
⤷ pKi 8.1 – 9.2 [41,43]
BRL 44408 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 8.8 pKi 43,45
⤷ pKi 8.2 – 8.8 [43,45]
atipamezole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 pKi 41
⤷ pKi 8.5 [41]
rauwolscine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 43
⤷ pKi 8.4 [43]
phentolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 pKi 4,8
⤷ pKi 8.4 [4,8]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist 8.3 pKi 6
⤷ pKi 8.3 (Ki 5x10-9 M) [6]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 – 8.9 pKi 4,8,43
⤷ pKi 7.6 – 8.9 [4,8,43]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.0 pKi 32
⤷ pKi 8.0 [32]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 pKi 32
⤷ pKi 7.9 [32]
mirtazapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.7 pKi 13
⤷ pKi 7.7 (Ki 2x10-8 M) [13]
Description: Inhibition of [3H]rauwolscine binding.
lurasidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.4 pKi 18
⤷ pKi 7.4 (Ki 4.07x10-8 M) [18]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 pKi 43
⤷ pKi 7.3 [43]
idazoxan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.2 pKi 41
⤷ pKi 7.2 [41]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 32
⤷ pKi 7.1 [32]
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 19
⤷ pKi 6.7 (Ki 1.99x10-7 M) [19]
Description: Inhibition of agonist-stimulated [35S]GTPγS binding
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.9 – 6.6 pKi 4,8
⤷ pKi 5.9 – 6.6 [4,8]
ARC-239 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.5 – 6.8 pKi 4,8,43
⤷ pKi 5.5 – 6.8 [4,8,43]
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 4,8,43
⤷ pKi 5.3 – 6.5 [4,8,43]
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 4.8 pKi 6
⤷ pKi 4.8 (Ki 1.4x10-5 M) [6]
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 22
⤷ pIC50 7.1 (IC50 8.511x10-8 M) [22]
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 [7].
Other agents that have a five-fold or greater lower affinity for the α2D include WB 4101, oxymetazoline, SKF 104078, raubasine and chlorpromazine [36]).
In binding assays, affinities are dependent on buffer condidtions [7].
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 26,44
⤷ pKd 2.5 [26,44]
ethylisopropylamiloride Small molecule or natural product Click here for species-specific activity table Hs Positive 1.8 pKd 44
⤷ pKd 1.8 [44]
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0001819 positive regulation of cytokine production IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
click arrow to show/hide IEA associations
GO:0002526 acute inflammatory response IEA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Potassium channel
Calcium channel
Phospholipase A2 stimulation
References:  5,20,27
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  11
Tissue Distribution Click here for help
Brain > spleen > kidney > aorta = lung = skeletal muscle > heart = liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  12,39
Brain > spleen = kidney = aorta > lung = skeletal muscle.
Absent in heart and liver.
Species:  Rat
Technique:  RNAse protection of mRNA.
References:  3,14
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:  5
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:  10,33
Physiological Functions Click here for help
Hypotension.
Species:  Mouse
Tissue:  CNS.
References:  21,31
Sedation.
Species:  Mouse
Tissue:  CNS.
References:  17,21,24
Analgesia.
Species:  Mouse
Tissue:  Brain.
References:  17,21,24
Hypothermia.
Species:  Mouse
Tissue:  CNS.
References:  17,21
Anesthetic-sparing effect.
Species:  Mouse
Tissue:  CNS.
References:  21,24
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Vasa deferens, heart.
References:  1,15,21
Physiological Consequences of Altering Gene Expression Click here for help
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:  1
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:  15
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:  37
The hypotensive effects of α2A agonists are abolished in α2A-adrenoceptor knockout mice.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  16
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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1. Altman JD, Trendelenburg AU, MacMillan L, Bernstein D, Limbird L, Starke K, Kobilka BK, Hein L. (1999) Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice. Mol Pharmacol, 56 (1): 154-61. [PMID:10385696]

2. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

3. Blaxall HS, Hass NA, Bylund DB. (1994) Expression of alpha 2-adrenergic receptor genes in rat tissues. Receptor, 4 (3): 191-9. [PMID:7812219]

4. 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]

5. 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 (2): 640-4. [PMID:2553931]

6. Carr BJ, Mihara K, Ramachandran R, Saifeddine M, Nathanson NM, Stell WK, Hollenberg MD. (2018) Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro. Invest Ophthalmol Vis Sci, 59 (7): 2778-2791. [PMID:29860464]

7. 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 (3): 1215-27. [PMID:8819505]

8. 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 (1): 43-9. [PMID:7908642]

9. Diamanti E, Del Bello F, Carbonara G, Carrieri A, Fracchiolla G, Giannella M, Mammoli V, Piergentili A, Pohjanoksa K, Quaglia W et al.. (2012) Might the observed α(2A)-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations?. Bioorg Med Chem, 20 (6): 2082-90. [PMID:22341244]

10. Docherty JR. (1998) Subtypes of functional alpha1- and alpha2-adrenoceptors. Eur J Pharmacol, 361 (1): 1-15. [PMID:9851536]

11. 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 (22): 15795-801. [PMID:1322406]

12. 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 (1): 70-5. [PMID:7688069]

13. Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005) Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem, 48 (6): 1709-12. [PMID:15771415]

14. Handy DE, Flordellis CS, Bogdanova NN, Bresnahan MR, Gavras H. (1993) Diverse tissue expression of rat alpha 2-adrenergic receptor genes. Hypertension, 21 (6 Pt 1): 861-5. [PMID:7684725]

15. Hein L, Altman JD, Kobilka BK. (1999) Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature, 402 (6758): 181-4. [PMID:10647009]

16. Hein L, Limbird LE, Eglen RM, Kobilka BK. (1999) Gene substitution/knockout to delineate the role of alpha 2-adrenoceptor subtypes in mediating central effects of catecholamines and imidazolines. Ann N Y Acad Sci, 881: 265-71. [PMID:10415924]

17. Hunter JC, Fontana DJ, Hedley LR, Jasper JR, Lewis R, Link RE, Secchi R, Sutton J, Eglen RM. (1997) Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice. Br J Pharmacol, 122 (7): 1339-44. [PMID:9421280]

18. Ishibashi T, Horisawa T, Tokuda K, Ishiyama T, Ogasa M, Tagashira R, Matsumoto K, Nishikawa H, Ueda Y, Toma S et al.. (2010) Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther, 334 (1): 171-81. [PMID:20404009]

19. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM. (1998) Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol, 55 (7): 1035-43. [PMID:9605427]

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