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α1A-adrenoceptor

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Target not currently curated in GtoImmuPdb

Target id: 22

Nomenclature: α1A-adrenoceptor

Family: Adrenoceptors

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 7 466 8p21.2 ADRA1A adrenoceptor alpha 1A
Mouse 7 466 14 D1 Adra1a adrenergic receptor, alpha 1a
Rat 7 466 15p12 Adra1a adrenoceptor alpha 1A
Previous and Unofficial Names Click here for help
α1c | α1a | ADRA1C | ADRA1L1 | adrenergic alpha 1c receptor | adrenergic receptor alpha 1c | alpha 1A-adrenoceptor | alpha 1A-adrenoreceptor | alpha 1C-adrenergic receptor | alpha-1A adrenergic receptor | adrenergic receptor, alpha 1a
Database Links Click here for help
Specialist databases
GPCRdb ada1a_human (Hs), ada1a_mouse (Mm), ada1a_rat (Rn)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline
Potency order of endogenous ligands (Human)
(-)-noradrenaline = (-)-adrenaline

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
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 Full agonist 7.2 – 8.2 pKi 23,32,52,93,101,115,122,129
pKi 7.2 – 8.2 [23,32,52,93,101,115,122,129]
dabuzalgron Small molecule or natural product Hs Agonist 7.4 pKi 13
pKi 7.4 [13]
A61603 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.8 – 7.5 pKi 23,32,35,65,101
pKi 6.8 – 7.5 [23,32,35,65,101]
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.5 pKi 101
pKi 6.5 [101]
cirazoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 – 6.7 pKi 32,101
pKi 6.2 – 6.7 [32,101]
NS-49 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.2 pKi 93
pKi 6.2 [93]
(-)-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 5.1 – 6.5 pKi 52,101,115,122
pKi 5.1 – 6.5 [52,101,115,122]
(-)-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 4.8 – 6.4 pKi 23,32,52,101,115,122,129
pKi 4.8 – 6.4 [23,32,52,101,115,122,129]
phenylephrine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 4.9 – 5.4 pKi 23,32,101,129
pKi 4.9 – 5.4 [23,32,101,129]
(+)-adrenaline Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.0 pKi 115
pKi 5.0 [115]
methoxamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 4.6 – 5.2 pKi 23,32,101,115,122,129
pKi 4.6 – 5.2 [23,32,101,115,122,129]
A61603 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.5 – 10.3 pEC50 23,32,65,101
pEC50 7.5 – 10.3 [23,32,65,101]
oxymetazoline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.2 – 9.3 pEC50 23,32,101
pEC50 7.2 – 9.3 [23,32,101]
cirazoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 – 9.2 pEC50 32,101
pEC50 6.9 – 9.2 [32,101]
naphazoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.6 – 8.9 pEC50 101
pEC50 6.6 – 8.9 [101]
(-)-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 5.6 – 9.1 pEC50 101
pEC50 5.6 – 9.1 [101]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.5 – 8.6 pEC50 23,32,101
pEC50 5.5 – 8.6 [23,32,101]
phenylephrine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 4.9 – 8.3 pEC50 23,32,101
pEC50 4.9 – 8.3 [23,32,101]
methoxamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 4.4 – 8.1 pEC50 23,32,101
pEC50 4.4 – 8.1 [23,32,101]
Agonist Comments
The first α1A-adrenoceptor to be cloned was the bovine homolog. No species significant differences in pharmacology have been identified.
The approved drug oxymetazoline displays α1A-AR selectivity but profile is complicated by significant actions at α2-AR and 5HT1B receptors [23]. This does not preclude clinically relevant activity at other adrenoceptors. A61603 is highly selective for the α1A-AR [23,32,101].

Note that EC50 values have been determined in a variety of assay formats measuring intracellular Ca2+ release, ERK1/2 phosphorylation, extracellular acidification rate and cAMP accumulation.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
olanzapine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 7.4 pA2 92
pA2 7.4 [92]
Description: Measured as antagonism of phenylephrine-induced contraction of endothelium-denuded rat small mesenteric artery.
[125I]HEAT (BE2254) Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.7 – 9.9 pKd 80,93,122
pKd 9.7 – 9.9 [80,93,122]
[3H]prazosin Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Inverse agonist 9.1 pKd 102
pKd 9.1 [102]
NAN 190 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.1 pKi 146
pKi 10.1 [146]
tamsulosin 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 Antagonist 9.4 – 10.7 pKi 17,24,35,102,104,115,122,138
pKi 9.4 – 10.7 [17,24,35,102,104,115,122,138]
silodosin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.6 – 10.4 pKi 102,104,122
pKi 9.6 – 10.4 [102,104,122]
WB 4101 Small molecule or natural product Rn Antagonist 9.5 – 10.2 pKi 54,134
pKi 9.5 – 10.2 [54,134]
upidosin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 35
pKi 9.6 [35]
RS-100329 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 102,138
pKi 9.6 [102,138]
S(+)-niguldipine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 – 10.0 pKi 35,102,122
pKi 9.1 – 10.0 [35,102,122]
prazosin Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inverse agonist 9.5 pKi 134
pKi 9.5 [134]
prazosin 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 Inverse agonist 9.0 – 9.9 pKi 17,24,35,102,122,138
pKi 9.0 – 9.9 [17,24,35,102,122,138]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.0 – 9.8 pKi 17,24,35,102,122
pKi 9.0 – 9.8 [17,24,35,102,122]
ρ-Da1a Peptide Hs Antagonist 9.2 – 9.5 pKi 80,106
pKi 9.2 – 9.5 [80,106]
S(+)-niguldipine Small molecule or natural product Rn Antagonist 9.3 pKi 134
pKi 9.3 [134]
SNAP5089 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 – 9.4 pKi 50,70,102,135
pKi 8.8 – 9.4 [50,70,102,135]
5-methylurapidil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 – 9.2 pKi 17,35,70,102,113,122,146
pKi 8.9 – 9.2 [17,35,70,102,113,122,146]
5-methylurapidil Small molecule or natural product Rn Antagonist 9.0 pKi 134
pKi 9.0 [134]
Ro-70-0004 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKi 138
pKi 8.9 [138]
doxazosin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.4 – 9.3 pKi 48,102,104
pKi 8.4 – 9.3 (Ki 5.37x10-10 M) [48,102,104]
RS-17053 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 9.3 pKi 17,24,34-35,102
pKi 8.3 – 9.3 [17,24,34-35,102]
BODIPY FL-prazosin Small molecule or natural product Ligand is labelled Hs Inverse agonist 8.7 pKi 83
pKi 8.7 (Ki 2x10-9 M) [83]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 86
pKi 8.6 [86]
HEAT (BE2254) Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.6 pKi 102
pKi 8.6 [102]
A-119637 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 16
pKi 8.6 [16]
A-119637 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.6 pKi 16
pKi 8.6 [16]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 – 8.7 pKi 102,146
pKi 8.4 – 8.7 [102,146]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 86
pKi 8.5 [86]
A-123189 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.5 pKi 16
pKi 8.5 [16]
ritanserin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 146
pKi 8.4 [146]
(+)-cyclazosin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.9 – 8.9 pKi 39,102
pKi 7.9 – 8.9 [39,102]
A-123189 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 16
pKi 8.4 [16]
indoramin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 pKi 24,35,102
pKi 8.4 [24,35,102]
phentolamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.2 – 8.6 pKi 102,122
pKi 8.2 – 8.6 [102,122]
carvedilol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 pKi 102
pKi 8.4 [102]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.3 pKi 146
pKi 8.3 [146]
terazosin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.9 – 8.7 pKi 84,102,104
pKi 7.9 – 8.7 (Ki 2x10-9 M) [84,102,104]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.1 – 8.3 pKi 102,146
pKi 8.1 – 8.3 [102,146]
ketanserin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 146
pKi 8.2 [146]
amitriptyline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 102
pKi 8.2 [102]
nortriptyline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.2 pKi 102
pKi 8.2 [102]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.9 – 8.3 pKi 86,102
pKi 7.9 – 8.3 [86,102]
phentolamine Small molecule or natural product Approved drug Rn Antagonist 8.1 pKi 134
pKi 8.1 [134]
clomipramine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.1 pKi 102
pKi 8.1 [102]
alfuzosin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.8 – 8.1 pKi 50,102,104
pKi 7.8 – 8.1 (Ki 8.2x10-9 M) [50,102,104]
KMUP-1 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 pKi 76
pKi 7.7 [76]
mianserin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.6 pKi 146
pKi 7.6 [146]
cyproheptadine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pKi 146
pKi 7.4 [146]
labetalol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.3 pKi 101
pKi 7.3 [101]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 – 7.3 pKi 102,146
pKi 6.9 – 7.3 [102,146]
BMY-7378 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 16
pKi 7.0 [16]
BMY-7378 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 7.0 pKi 16,102,146
pKi 6.6 – 7.0 [16,102,146]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.5 pKi 86
pKi 6.5 [86]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 86
pKi 6.1 [86]
labetalol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 – 7.9 pIC50 101
pIC50 7.5 – 7.9 [101]
View species-specific antagonist tables
Antagonist Comments
Compounds such as prazosin and RS-17053 show unexpectedly low potency in certain isolated tissue assays [34-35]. This was postulated to result from a novel α1- adrenoceptor subtype (α1L), but is now thought to result from differences in α1A-AR characteristics dependent on the tissue or assay environment [42,136]. Silodosin, niguldipine, SNAP5089, RS-100329 and Ro-70-0004 are selective for α1A-ARs over the α1B- and α1D-AR subtypes [102,138]. The insurmountable antagonist ρ-Da1a is also α1A-AR subtype selective. Some antidepressants such as amitriptyline and clomipramine are selective for α1A-AR vs. other α1-AR subtypes [102]. BMY-7378 is a partial agonist in some systems [101]. Phenoxybenzamine is an irreversible α1-AR antagonist used to block the pressor effects of catecholamines prior to surgery for phaeochromocytoma. Doxazosin, alfuzosin, prazosin, tamsulosin, terazosin and cyclazosin are selective for α1-ARs vs. α2-ARs. Lisuride behaves as a partial agonist in some systems [101]. Compounds designated as "partial inverse agonists" [85] are listed as neutral antagonists. Bodipy FL-prazosin (QAPB) has been used to examine the cellular localisation of α1-adrenoceptors. Carvedilol is regarded as predominantly a β-AR antagonist, and it is this property that is primarily responsible for its usefulness in treating cardiac failure but it also potently inhibits α1-AR. It is somewhat selective for α1A-AR. Labetalol has similar properties but is less potent and is considered safe for use in pregnancy to treat eclampsia and pre-eclampsia. It also behaves as a partial agonist in some systems.
Allosteric Modulators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
rho-TIA Peptide Click here for species-specific activity table Rn Negative 5.0 pKi 116
pKi 5.0 (Ki 1x10-5 M) [116]
Allosteric Modulator Comments
Whilst diazepam reduces the potency of phenylephrine to stimulate the inositol phosphate (IP) response in Rat-1 fibroblasts expressing the α1A-AR, no change in the maximum IP response is observed. In contrast, the maximum IP response to clonidine (a weak partial agonist at α1A-AR) is increased by diazepam, midazolam and lorazepam, suggesting that the ability to detect allosteric potentiation is a function of both the intrinsic activity of the α1-AR agonist and the activity of the proposed modulator [133]. Data published by Williams et al. (2018) show that diazepam is not a direct allosteric modulator of α1-adrenoceptors [137], but is able to modulate receptor activity via inhibition of phosphodiesterase 4.

Amiloride analogues increase the dissociation rate of prazosin from the α1A-adrenoceptor [46].

Possible allosteric inhibition has been shown with ρ-TIA, a member of the ρ-conopeptide class of toxins derived from cone snails. ρ-TIA acts as an α1-adrenoceptor antagonist and is able to inhibit the norepinephrine-evoked increases in cytosolic-free calcium concentration and contractility. N-terminally truncated ρ-TIA analogues are less active than the full-length peptide. Upon deletion of the fourth residue of full-length ρ-TIA (in the form of the analogue TIA5-19), antagonist activity is observed at 65% compared to the response observed in full length ρ-TIA [116].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Calcium channel
Other - See Comments
Comments:  The α1A-adrenoceptor is coupled to calcium release and inositol phosphate production (i.e. to Gq) more efficiently than the other α1-AR subtypes.

The α1A-adrenoceptor is coupled to activation and translocation of Snapin and the TRPC6 channel to the plasma membrane and subsequent increase in Calcium entry and contractility.
References:  46,85
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
G12/G13 family Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  α1-adrenoceptors (all subtypes) can also activate protein kinase C, mitogen activated protein kinases.
G13 coupling observed in transfected CHO cells to regulate arachidonic acid release.
PKCzeta coupling to phospholipase D observed in transfected rat-1 fibroblasts.
α1A- and α1B-adrenoceptors also couple to adenylyl cyclase to increase cAMP [23,101] but agonists have low potency.
References:  46,63,85,99
Tissue Distribution Click here for help
Cauda epididymis.
Species:  Human
Technique:  RT-PCR, receptor binding, inhibition of contraction by selective antagonists.
References:  96
In the human brain, the highest levels of α1A message are found in olfactory system, hypothalamic nuclei and in regions of the brainstem and spinal cord related to motor function. Also expressed in the hippocampus.
Species:  Human
Technique:  in situ hybridisation (including oligonucleotide labelling)
References:  27,126
Dissociated, prostatic smooth muscle cells- plasmalemmal membrane and on intracellular compartments.
Species:  Human
Technique:  Confocal microscopy.
References:  78
High expression levels of α1A-adrenoceptor mRNA are found in the heart, liver, cerebellum and cerebral cortex.
Species:  Human
Technique:  RNase protection assay
References:  100
Prostate
Species:  Human
Technique:  Northern blot, RT PCR, receptor binding
References:  33
Bladder and urethra.
Species:  Human
Technique:  RT PCR, receptor binding
References:  123
Lymphocytes, saphenous vein.
Species:  Human
Technique:  in situ hybridisation
References:  130,143
The α1A-adrenoceptor is the predominant subtype in human prostate and urethra.
Species:  Human
Technique:  Immunohistochemistry.
References:  132
Bladder and urethra.
Species:  Mouse
Technique:  RT PCR, functional responses
References:  6
Glucose uptake into fat, skeletal muscle and heart
Species:  Mouse
Technique:  KO mice and mice expressing a constitutively active α1A-adrenoceptor
References:  121
Expressed in various neurons in the cerebral cortex, hippocampus, hypothalamus, midbrain, cerebellum, spinal cord; GABAergic interneurons and NG2 oligodendrocyte progenitors.
Species:  Mouse
Technique:  Systemic promoter-GFP transgenic model, RT PCR, receptor binding.
References:  18,97
Epididymis.
Species:  Rat
Technique:  Radionucleotide binding, ribonuclease protection assay
References:  105
Renal resistance arteries.
Species:  Rat
Technique:  Radioligand binding
References:  110
Proximal and distal tail artery.
Species:  Rat
Technique:  RT-PCR and functional studies with selective agonists and antagonists
References:  62
Prefrontal cortex.
Species:  Rat
Technique:  in situ hybridisation.
References:  111
Taste buds, left ventricle, aorta, tail and mesenteric arteries.
Species:  Rat
Technique:  RT-PCR
References:  10,79,150
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
α1A-AR differentially couples to STAT3 phosphorylation through PKC epsilon and delta.
Species:  Mouse
Tissue:  Cardiomyocytes.
Response measured:  Receptor coupling to STAT3, JAK2 and SRC.
References:  119
Nuclear α1A-ARs activated ERK localized to caveolae at plasma membrane and receptor oligomerization.
Species:  Mouse
Tissue:  Cardiomyocytes.
Response measured:  Nuclear localization/co-localization, ERK1/2 signaling.
References:  140-141
RGS2 interacts with α1A-AR third intracellular loop to inhibit signal transduction.
Species:  Human
Tissue:  Transfected HEK 293 cells.
Response measured:  Receptor/RGS2 association, IP3 accumulation, radioligand binding.
References:  45
α1A-AR mediated p90 ribosomal S6 kinase activation increases early gene regulation.
Species:  Rat
Tissue:  Heart.
Response measured:  Cardiomyocyte gene expression, pERK1/2, pRSK, cardiomyocyte transcriptome
References:  9
Constitutive internalisation of the α1A-AR.
Species:  Rat
Tissue:  Transfected Rat-1 fibroblasts.
Response measured:  Receptor traffiking with HA tagged α1A-AR/GFP fusion protein, IP3 accumulation.
References:  90
α1A-AR coupling to G proteins is required for second messenger, mitogenic and transcriptional responses.
Species:  Human
Tissue:  Transfected PC12 cells.
Response measured:  G-protein coupling: calcium and inositol phosphate responses, MAK kinase activity, tyrosine kinase Pyk2 activity and transcriptional responses.
References:  69
α1A-AR regulates the secretion of extracellular matrix, cell adhesion and migration.
Species:  Rat
Tissue:  Rat-1 fibroblasts stably transfected with human α1A-AR.
Response measured:  Secretion of hyaluronan, CD44, IL-6, syndecan-4, tenascin-C, increases in cell adhesion and inhibition of cell migration, microarray analysis, PCR.
References:  117
Extracellular loop residues required for α1-AR subtype binding.
Species:  Rat
Tissue:  Transfected COS-1 cells.
Response measured:  Radioligand binding: Q177G, I178V, N179T α1A-AR mutations decrease binding affinity for phentolamine and WB4101.
References:  151
Role of serine interactions for α1A-AR binding and activation.
Species:  Rat
Tissue:  Transfected COS-1 cells.
Response measured:  Radioligand binding, inositol phosphate production, site directed mutagenesis.
References:  57
M292L mutation in the α1A-AR causes constitutive activity.
Species:  Rat
Tissue:  Transfected COS-1 cells.
Response measured:  Phospholipase C and phospholipase A2 activity and agonist potency.
References:  56
α1A-AR differentiates fibroblasts to smooth muscle, induces hypertrophy and cell cycle arrest and alters p27, p21, pRb, cyclin D1, cdk2 & 4, pcna.
Species:  Rat
Tissue:  Transfected rat-1 fibroblasts.
Response measured:  Diffferentiation, hypertrophy and cell cycle arrest.
References:  109
Androgen effects on α1A-AR subtypes in rat seminal vesicle contractile responses.
Species:  Rat
Tissue:  Seminal vesicles.
Response measured:  mRNA by ribonuclease protection, contraction.
References:  82
α1A-AR is the major subtype involved in norepinephrine-induced contraction of mouse ureter.
Species:  Mouse
Tissue:  Isolated ureteral preparations.
Response measured:  mRNA expression, inhibition of norepinephrine mediated contractions by subtype selective α1-AR antagonists.
References:  67
Activation of α1A-AR increases cardiomyocyte shortening and increases myofilament Ca2+ sensitivity which is potentiated by propofol.
Species:  Rat
Tissue:  Primary ventricular cardiomyocytes.
Response measured:  Contraction, Ca2+ levels.
References:  37
Role of α1A-AR in post infarct remodelling, dysfunction and survival.
Species:  Mouse
Tissue:  Heart muscle.
Response measured:  Cardiac specific over expression of α1A-AR (rat), LV shortening, dP/dtmax
References:  30
Isolated Vas deferens.
Species:  Rat
Tissue:  Prostatic and epididymal Vas deferens.
Response measured:  Contraction, [3H]prazosin binding.
References:  94
Pleiotropism of the α1A-AR
Species:  Human
Tissue:  Prostate
Response measured:  Contraction, [3H]prozosin binding, IP3 accumulation.
References:  35
Cell cycle arrest.
Species:  Rat
Tissue:  Transfected Rat-1 fibroblasts.
Response measured:  Activities of CDK-6, cyclin E-associated kinase and cell cycle kinase inhibitor p27Kip1.
References:  40
Heteromeric complex formation between atypical chemokine receptor 3 and α1A-AR.
Species:  Human
Tissue:  hVSMC, HEK293 or CHO cells
Response measured:  Proximity ligation assay, BRET
References:  5,31,38,91
Allosteric modulation of α1A-AR by 9-aminoacridine compounds.
Species:  Human
Tissue:  Transient transfection of COS1 cells.
Response measured:  [3H]prazosin binding, IP3 accumulation
References:  15
α1A-AR endocytic pathway involves ERK but not Gq/PLC/PKC signaling.
Species:  Human
Tissue:  Transfected HEK 293 cells.
Response measured:  ERK 1/2 phosphorylation.
References:  77
α1A-AR is a lipid raft protein and mediates signaling from rafts but exits rafts for internalization through clathrin-coated pits.
Species:  Rat
Tissue:  Rat-1 fibroblasts expressing α1A-AR.
Response measured:  Fluorescence resonance energy transfer and confocal measurement of receptor distribution and internalization.
References:  89
Biased agonism at α1A-AR.
Species:  Human
Tissue:  Stably transfected CHO-K1 cells
Response measured:  Cell membrane [125I]HEAT binding, Ca2+ mobilisation, cAMP accumulation, ERK1/2 phosphorylation, ECAR.
References:  23,32
Selectivity of α-adrenoceptor agonists for the human α1A, α1B- and α1D-adrenoceptors.
Species:  Human
Tissue:  Stably transfected CHO-K1 cells
Response measured:  Whole cell [3H]prazosin binding, Ca2+ mobilisation, cAMP accumulation, ERK1/2 phosphorylation
References:  101
The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors
Species:  Human
Tissue:  Stably transfected CHO-K1 cells
Response measured:  Whole cell [3H]prazosin binding
References:  102
Determination of the functional α1A-AR phenotype mediating contraction of human contractile tissue.
Species:  Human
Tissue:  Erectile tissue, vas deferens.
Response measured:  [3H]tamsulosin binding, inhibition of noradrenaline mediated contractions by subtype-selective antagonists.
References:  25-26
Selective insurmountable antagonism of α1A-AR by green mamba venom ρ-Da1a.
Species:  Human
Tissue:  CHO-K1 cells stably expressing human α1A-AR.
Response measured:  [3H]prazosin, [125I]HEAT binding, agonist stimulated Ca2+ mobilisation
References:  80
Determinants of agonist binding to the α1A-AR.
Species:  Rat
Tissue:  Transiently transfected COS-1 cells.
Response measured:  Radioligand binding, site directed mutagenesis.
References:  55,81
Role of α1A-AR in cardiac contractility.
Species:  Mouse
Tissue:  Heart muscle.
Response measured:  Contractile function, Ca2+ levels, Snapin, TRPC1, TRPC6 levels, cardiac specific over expression of α1A-AR (rat).
References:  87
Anti-apoptotic and protective effects of α1A-AR in cardiac ischaemia.
Species:  Mouse
Tissue:  Cardiac myocytes and HL-1 cells
Response measured:  [3H]deoxyglucose uptake, GLUT4 translocation
References:  120
Physiological Functions Click here for help
Contraction of stromal and capsular smooth muscle to control urethral resistance.
Species:  Human
Tissue:  Prostate.
References:  51
Contraction of urethral smooth muscle.
Species:  Human
Tissue:  Urethra.
References:  128
Contraction of skeletal muscle resistance arteries.
Species:  Human
Tissue:  Vasculature.
References:  60
Glucose uptake in heart.
Species:  Rat
Tissue:  Cardiomyocyte
References:  112
Orthostatic hypotensive effect of antipsychotic drugs is mediated by α1A-AR.
Species:  Rat
Tissue:  Mesenteric arteries.
References:  92
Activation of sarcolemmal Na+-H+ exchanger.
Species:  Rat
Tissue:  Ventricular myocytes.
References:  124
Silodosin (KM-3213: an α1A-AR selective antagonist) can improve the lower urinary tract symptoms associated with benign prostatic hyperplasia.
Species:  Human
Tissue:  Lower urinary tract.
References:  114
Decreased α1A-AR mRNA in renal tissue during aging.
Species:  Rat
Tissue:  Kidney.
References:  71
Contraction of right gastroepiploic artery.
Species:  Human
Tissue:  Artery.
References:  47
Contractile responses in human subcutaneous arteries.
Species:  Human
Tissue:  Subcutaneous arteries.
References:  59
Estrogen down-regulates α1A-AR expression in the urethral smooth muscle of female rats.
Species:  Rat
Tissue:  Intact urethra and isolated urethral smooth muscle cells.
References:  12
Stimulation of myocyte hypertrophy.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  66
Inhibition of outward current via the acid-sensitive potassium channel TASK-1 by α1A-AR.
Species:  Rat
Tissue:  Heart.
References:  103
Contraction of anal sphincter.
Species:  Human
Tissue:  Anal sphincter
References:  95
Contraction of cauda epididymis.
Species:  Rat
Tissue:  Cauda epididymis
References:  96
The involvement of urothelial α1A-AR in controlling the micturition reflex.
Species:  Rat
Tissue:  Bladder.
References:  144
Interaction between H2S, NO and α1A-AR signalling in kidney of rats with left ventricular hypertrophy
Species:  Rat
Tissue:  Kidney
References:  2-3
Activation of bladder mechanosensory A delta fibres.
Species:  Rat
Tissue:  Bladder
References:  4
Role of α1A-AR in contraction of urethral smooth muscle in males and females.
Species:  Mouse
Tissue:  Urethra
References:  6
Phasic responses of portal vein.
Species:  Rat
Tissue:  Portal vein
References:  7
Effect of ageing and hypertension on desensitisation of vasoconstriction.
Species:  Rat
Tissue:  Aorta, tail and mesenteric arteries, responses and gene expression.
References:  10
Trafficking of aquaporin-5 in salivary glands.
Species:  Rat
Tissue:  Salivary glands
References:  14
Improved function and survival in heart failure.
Species:  Mouse
Tissue:  Ventricle
References:  21-22
Inotropic response in the failing heart.
Species:  Human
Tissue:  Ventricular trabeculae
References:  58
Role of α1A-AR in migration and gene expression in fibroblasts.
Species:  Human
Tissue:  Skin fibroblasts
References:  73
Anti-apoptotic and protective effects in heart.
Species:  Mouse
Tissue:  Cardiomyocyte
References:  120-121,139
Vascular tone.
Species:  Mouse
Tissue:  Femoral artery
References:  148
Regulation and development of ovarian function.
Species:  Rat
Tissue:  Ovary- granulosa cells
References:  145
Facilitates GABA release in the basolateral nucleus of the amygdala to mediate antiepileptic properties of norepinephrine.
Species:  Rat
Tissue:  Brain.
References:  11
Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different α1-adrenoceptor subtypes.
Species:  Rat
Tissue:  Aorta.
References:  149
Activation of α1A-AR promotes differentiation of rat-1 fibroblasts to a smooth muscle-like phenotype.
Species:  Rat
Tissue:  Transfected rat-1 fibroblasts.
References:  109
α1A-AR inhibits PDGF receptor Tyr751 phosphorylation and PI3K activation.
Species:  Human
Tissue:  Transfected Rat-1 fibroblasts.
References:  75
Altered adrenoceptor signaling following traumatic brain injury contributes to working memory dysfunction.
Species:  Rat
Tissue:  Brain (prefrontal cortex).
References:  68
NOS inhibition by L-NNA abolishes cardioprotective effects of α1A-adrenoceptor.
Species:  Rat
Tissue:  Heart.
References:  153
Physiological Consequences of Altering Gene Expression Click here for help
Hypotension and a decreased pressor response to phenylephrine in α1A-AR knockout mice.
Species:  Mouse
Tissue:  In vivo.
Technique:  Transgenesis.
References:  107
α1A-AR regulates ERK survival pathway and decreases apoptosis in adult myocytes.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockouts.
References:  53
Mice with systemic constitively active mutation (CAM) have increased adult neurogenesis and gliogenesis.
Species:  Mouse
Tissue:  Brain, adult neural stem cells.
Technique:  Gene over-expression.
References:  44
Mice with systemic constitively active mutation (CAM) of the α1A-AR are preconditioned against ischemia through PKC mechanism.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  108
Receptor over-expression inhibits Ins(1,4,5)P3 generation despite elevated PLC, measured as elevated p-MEK and p-ERK protein levels.
Species:  Mouse
Tissue:  Heart
Technique:  Gene over-expression.
References:  8
Cardioprotection in rats with α1A-adrenoceptor overexpression resembles that in non-transgenic littermates with preconditioning mediated by iNOS activation.
Species:  Rat
Tissue:  Heart.
Technique:  Gene over-expression.
References:  153
Cardiac specific overexpression of α1A-AR enhances cardiac contractility without hypertrophy.
Species:  Mouse
Tissue:  Heart.
Technique:  Transgenesis.
References:  74
Mice with systemic constitively active mutation (CAM) have increased synaptic plasticity, cognition and longevity.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene over-expression.
References:  28
Mice with systemic constitively active mutation (CAM) of the α1A-AR have reduced incidence of cancer.
Species:  Mouse
Tissue:  In vivo.
Technique:  Expression of CAM α1A-AR.
References:  19
Skin fibroblast migration, TGFβ1, IGF-1, HA and PIP production in response to α1A-AR stimulation, are inhibited by treatment of α1A-AR siRNA
Species:  Human
Tissue:  Skin fibroblasts.
Technique:  Gene knockdown with siRNA.
References:  73
Increased post MI hypertrophy, ventricular dilatation, fibrosis, apoptosis and mortality in α1A-AR knockout mice.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockout.
References:  145
Following coronary artery occlusion, rats with cardiomyocyte-specific α1A-AR over-expression display less fibrosis, hypertrophy and lung weight and show preserved LV ejection fraction compared to non-transgenic littermates
Species:  Rat
Tissue:  Heart.
Technique:  Cardiomyocyte specific α1A-AR over-expression.
References:  152
α1A-AR mediated inotrophy in failing RV myocardium requires the α1A-AR.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockout.
References:  20
α1A-AR activation is anti-apoptotic and protective related to enhanced glucose uptake into the heart.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  120
α1A-AR activation promotes a favourable metabolic phenotype.
Species:  Mouse
Tissue:  Fat, skeletal muscle, heart, plasma.
Technique:  Gene knockout and expression of CAM mutant.
References:  121
Cardiac-specific over-expression of α1A-AR increases expression of relaxin receptor RXFP1.
Species:  Mouse
Tissue:  Heart.
Technique:  Cardiomyocyte specific over expression of α1A-AR.
References:  88
Down-regulation of α1A-AR attenuates ocular inflammation by inhibiting permeability of the blood brain barrier.
Species:  Mouse
Tissue:  Eye.
Technique:  Exposure to light, blood flow, flow cytometry, PCR, immunohistochemistry.
References:  125
Disruption of α1A/B-AR/CXCR4 heteromers inhibits α1A-AR function in vascular smooth muscle cells (human and rat).
Species:  Human
Tissue:  Vascular smooth muscle cells.
Technique:  siRNA gene silencing, proximity ligation assay, Ca2+ influx, contraction.
References:  131
α1A-AR counterbalance pathological pathways during post MI remodelling.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockout.
References:  145
Pleiotropic α1A-AR signalling inhibits RhoA/ROCK activity and contractility*.
Species:  Mouse
Tissue:  Heart.
Technique:  Cardiomyocyte specific over expression of α1A-AR. *α1A-AR agonist in cardiac restricted α1A-AR over expressing mice enhances contractility without hypertrophy
References:  147
Cardiac hypertrophy: mice with systemic constitively active mutation (CAM) of the α1A-AR secrete IL-6 and develop cardiac hypertrophy independently of changes in blood pressure. Co-activation of both α1A- and α1B-ARs inhibits development of hypertrophy.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  98
Mice with α1A-AR over-expression develop a hypercontractile inotropic phenotype: hypercontraction and high fractional shortening.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  29
Increased p-MEK and p-ERK in rats with α1A-adrenoceptor overexpression.
Species:  Rat
Tissue:  Heart.
Technique:  Gene over-expression.
References:  153
Xenobiotics Influencing Gene Expression Click here for help
Peroxynitrite generated through septic shock (bacterial infection) can inhibit noradrenaline-induced contraction in rat endothelium-denuded aorta strips which contain α1A- and α1D-AR subtypes and represents a possible contributory mechanism underlying systemic hypotension in sepsis.
Species:  Rat
Tissue:  Endothelium-denuded aorta strips.
Technique:  Recording of tension changes in organ bath culture.