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α1A-adrenoceptor

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Target id: 22

Nomenclature: α1A-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 7 466 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 P35348 (Hs), P97718 (Mm), P43140 (Rn)
ChEMBL Target CHEMBL229 (Hs), CHEMBL2822 (Mm), CHEMBL319 (Rn)
DrugBank Target P35348 (Hs)
Ensembl Gene ENSG00000120907 (Hs), ENSMUSG00000045875 (Mm), ENSRNOG00000009522 (Rn)
Entrez Gene 148 (Hs), 11549 (Mm), 29412 (Rn)
Human Protein Atlas ENSG00000120907 (Hs)
KEGG Gene hsa:148 (Hs), mmu:11549 (Mm), rno:29412 (Rn)
OMIM 104221 (Hs)
Pharos P35348 (Hs)
RefSeq Nucleotide NM_000680 (Hs), NM_013461 (Mm), NM_017191 (Rn)
RefSeq Protein NP_000671 (Hs), NP_038489 (Mm), NP_058887 (Rn)
UniProtKB P35348 (Hs), P97718 (Mm), P43140 (Rn)
Wikipedia ADRA1A (Hs)
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline

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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 8.0 – 8.2 pKi 30,59,82,87
⤷ pKi 8.0 – 8.2 [30,59,82,87]
dabuzalgron Small molecule or natural product Hs Agonist 7.4 pKi 5
⤷ pKi 7.4 [5]
(-)-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 6.3 – 6.5 pKi 30,65,82
⤷ pKi 6.3 – 6.5 [30,65,82]
NS-49 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.2 pKi 59
⤷ pKi 6.2 [59]
(-)-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 5.8 – 6.4 pKi 9,15,30,65,82,87
⤷ pKi 5.8 – 6.4 [9,15,30,65,82,87]
phenylephrine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 5.2 – 5.4 pKi 87
⤷ pKi 5.2 – 5.4 [87]
methoxamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 5.0 – 5.2 pKi 82,87
⤷ pKi 5.0 – 5.2 [82,87]
(+)-adrenaline Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.0 pKi 82
⤷ pKi 5.0 [82]
A61603 Small molecule or natural product Hs Full agonist 7.8 – 8.4 pIC50 17,39
⤷ pIC50 7.8 – 8.4 [17,39]
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 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.
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 58
⤷ pA2 7.4 [58]
Description: Measured as antagonism of phenylephrine-induced contraction of endothelium-denuded rat small mesenteric artery.
[125I]HEAT Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.0 pKd 82
⤷ pKd 10.0 [82]
[125I]BE-2254 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.9 pKd 54,77
⤷ pKd 9.9 [54,77]
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 9.7 – 10.7 pKi 8,10,17,66,82,94
⤷ pKi 9.7 – 10.7 [8,10,17,66,82,94]
WB 4101 Small molecule or natural product Rn Antagonist 10.2 pKi 91
⤷ pKi 10.2 [91]
NAN 190 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.1 pKi 100
⤷ pKi 10.1 [100]
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 66,82
⤷ pKi 9.6 – 10.4 [66,82]
WB 4101 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.7 – 9.8 pKi 8,10,17,82
⤷ pKi 9.7 – 9.8 [8,10,17,82]
upidosin Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 17
⤷ pKi 9.6 [17]
RS-100329 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 66,94
⤷ pKi 9.6 [66,94]
S(+)-niguldipine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 – 10.0 pKi 17,66,82
⤷ pKi 9.1 – 10.0 [17,66,82]
prazosin Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inverse agonist 9.5 pKi 91
⤷ pKi 9.5 [91]
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 8,10,17,66,82,94
⤷ pKi 9.0 – 9.9 [8,10,17,66,82,94]
S(+)-niguldipine Small molecule or natural product Rn Antagonist 9.3 pKi 91
⤷ pKi 9.3 [91]
ρ-Da1a Peptide Hs Antagonist 9.2 – 9.3 pKi 50,69
⤷ pKi 9.2 – 9.3 [50,69]
SNAP5089 Small molecule or natural product Hs Antagonist 8.8 – 9.4 pKi 28,44,66,92
⤷ pKi 8.8 – 9.4 [28,44,66,92]
5-methylurapidil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 – 9.2 pKi 8,17,75,82,100
⤷ pKi 8.9 – 9.2 [8,17,75,82,100]
5-methylurapidil Small molecule or natural product Rn Antagonist 9.0 pKi 91
⤷ pKi 9.0 [91]
doxazosin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.6 – 9.3 pKi 27,66
⤷ pKi 8.6 – 9.3 (Ki 5.37x10-10 M) [27,66]
Ro-70-0004 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKi 94
⤷ pKi 8.9 [94]
RS-17053 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 – 9.3 pKi 8,10,16-17,66
⤷ pKi 8.3 – 9.3 [8,10,16-17,66]
roxindole Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 55
⤷ pKi 8.6 [55]
A-119637 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 7
⤷ pKi 8.6 [7]
A-119637 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.6 pKi 7
⤷ pKi 8.6 [7]
terguride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.5 pKi 55
⤷ pKi 8.5 [55]
A-123189 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.5 pKi 7
⤷ pKi 8.5 [7]
risperidone Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 100
⤷ pKi 8.4 [100]
ritanserin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 pKi 100
⤷ pKi 8.4 [100]
A-123189 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 7
⤷ pKi 8.4 [7]
indoramin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.4 pKi 10,17
⤷ pKi 8.4 [10,17]
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 66,82
⤷ pKi 8.2 – 8.6 [66,82]
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.3 pKi 55
⤷ pKi 8.3 [55]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.3 pKi 100
⤷ pKi 8.3 [100]
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 53,66
⤷ pKi 7.9 – 8.7 (Ki 2x10-9 M) [53,66]
ketanserin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.2 pKi 100
⤷ pKi 8.2 [100]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.1 pKi 100
⤷ pKi 8.1 [100]
phentolamine Small molecule or natural product Approved drug Rn Antagonist 8.1 pKi 91
⤷ pKi 8.1 [91]
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 28,66
⤷ pKi 7.8 – 8.1 (Ki 8.2x10-9 M) [28,66]
(+)-cyclazosin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.9 pKi 20
⤷ pKi 7.9 [20]
KMUP-1 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.7 pKi 47
⤷ pKi 7.7 [47]
mianserin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.6 pKi 100
⤷ pKi 7.6 [100]
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 100
⤷ pKi 7.4 [100]
spiroxatrine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 pKi 100
⤷ pKi 7.3 [100]
BMY-7378 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.0 pKi 7
⤷ pKi 7.0 [7]
BMY-7378 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 – 7.0 pKi 7,100
⤷ pKi 6.9 – 7.0 [7,100]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.5 pKi 55
⤷ pKi 6.5 [55]
piribedil Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 pKi 55
⤷ pKi 6.1 [55]
View species-specific antagonist tables
Antagonist Comments
Compounds such as prazosin and RS-17053 show unexpectedly low potency in certain isolated tissue assays (e.g. canine prostate) [28]. This was postulated to result from a novel α1- adrenoceptor subtype (α1L). It is now thought that this may result from differences in α1A-adrenoceptor characteristics dependent on tissue or assay environment [17].
RS-100329 and Ro-70-0004 are both 50-fold selective for α1A-adrenoceptors over the α1B- and α1D-adrenoceptor subtypes [94].
Doxazosin is selective for α1-adrenoceptors.
alfuzosin is an approved drug which is an antagonist of several α1-adrenoceptors.
Compounds designated as "partial inverse agonists" [54] are listed as neutral antagonists.
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 78
⤷ pKi 5.0 (Ki 1x10-5 M) [78]
Allosteric Modulator Comments
Whilst diazepam reduces the potency of phenylephrine to stimulate the 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 [90]. Data published by Williams et al. (2018) show that diazepam is not a direct allosteric modulator of α1-adrenoceptors [93], but is able to modulate receptor activity via inhibition of phosphodiesterase 4.

Amiloride analogs will increase the dissociation rate of prazosin from the α1A-adrenoceptor [25].

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 analog TIA5-19), antagonist activity is observed at 65% compared to the response observed in full length ρ-TIA.
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 more efficiently than the other 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:  25,54
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.
References:  25,38,54,63
Tissue Distribution Click here for help
Dissociated, prostatic smooth muscle cells- plasmalemmal membrane and on intracellular compartments.
Species:  Human
Technique:  Confocal microscopy.
References:  49
High expression levels of α1A-adrenoceptor mRNA are found in the heart, liver, cerebellum and cerebral cortex.
Species:  Human
Technique:  RNase protection assay
References:  64
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:  11,84
Lymphocytes, saphenous vein.
Species:  Human
Technique:  in situ hybridisation
References:  88,98
The α1A-adrenoceptor is the predominant subtype in human prostate and urethra.
Species:  Human
Technique:  Immunohistochemistry.
References:  89
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.
References:  61
Renal resistance arteries.
Species:  Rat
Technique:  Radioligand binding
References:  73
Epididymis.
Species:  Rat
Technique:  Radionucleotide binding, ribonuclease protection assay
References:  68
Prefrontal cortex.
Species:  Rat
Technique:  in situ hybridisation.
References:  74
Taste buds.
Species:  Rat
Technique:  RT-PCR
References:  102
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
Isolated longitudinal strip of Vas Deferens.
Species:  Rat
Tissue:  Vas deferens
Response measured:  Contraction
References:  60
Isolated strips of prostate tissue containing both glandular and smooth muscle elements.
Species:  Human
Tissue:  Prostrate
Response measured:  Contraction
References:  17
Blocks shortened intercontraction interval induced by excessive norepinephrine.
Species:  Rat
Tissue:  Bladder
Response measured:  Micturition reflex.
References:  99
Intima-media growth was blocked by KMD3213 (α1A-AR antagonist) and adventitial growth by AH11110A (α1B-AR antagonist), whereas BMY7378 (α1D-AR antagonist) had no effect.
Species:  Rat
Tissue:  Aorta.
Response measured:  Intima-media and adventitia DNA content, protein synthesis, and protein content measured as indicators of cell growth.
References:  101
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:  48
α1A-AR differentially couples to STAT3 phosphorylation through PKC epsilon and delta.
Species:  Mouse
Tissue:  Cardiomyocytes.
Response measured:  Receptor coupling to STAT3.
References:  81
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:  33
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:  24
Nuclear α1A-ARs activated ERK localized to caveolae at plasma membrane and receptor oligomerization.
Species:  Mouse
Tissue:  Cardiomyocytes.
Response measured:  Nuclear localization/co-localization.
References:  95-96
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:  72
α1A-AR mediated p90 ribosomal S6 kinase activation increases early gene regulation.
Species:  Rat
Tissue:  Heart.
Response measured:  Cardiomyocyte gene expression
References:  2
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:  24
α1A-AR is continuously internalized in the absence of agonist.
Species:  Rat
Tissue:  Transfected Rat-1 fibroblasts.
Response measured:  Receptor traffiking.
References:  57
Mutant that uncouples receptor from G-proteins also abolished all second messenger, mitogenic and transcriptional signals.
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:  43
α1A-AR inhibits PDGF- receptor Tyr 751 phosphorylation and PI3K activation.
Species:  Human
Tissue:  Transfected Rat-1 fibroblasts.
Response measured:  Coupling to PDGF-induced PI3K.
References:  6
Traumatic brain injury increases α1A-AR but not α1B-AR mRNA levels in prefrontal cortex and prazosin improved working memory performance.
Species:  Rat
Tissue:  Brain (prefrontal cortex).
Response measured:  α1A-AR mRNA expression.
References:  42
α1A-AR regulates the secretion of hyaluronan, CD44, IL-6, syndecan-4, tenascin-C and increases cell adhesion and inhibits cell migration.
Species:  Rat
Tissue:  Transfected Rat-1 fibroblasts.
Response measured:  Secretion of extracellular matrix, cell adhesion and migration.
References:  79
Q177G, I178V, N179T α1A-AR mutations decrease binding affinity for phentolamine and WB4101 to that of the α1B-AR subtype (ie conferring subtype-selective antagonist binding).
Species:  Rat
Tissue:  Transfected COS-1 cells
Response measured:  Radioligand binding.
References:  103
S188 and S192 inin transmembrane helix V of α1A-AR are involved in binding but only S188 is involved in activation.
Species:  Rat
Tissue:  Transfected COS-1 cells.
Response measured:  Radioligand binding, inositol phosphate production.
References:  34
Val185A, Met293L mutations in α1A-AR decreased affinity for agonist to that of the α1B-AR. L290F mutation decreases oxymetazoline affinity.
Species:  Rat
Tissue:  Transfected COS-1 cells.
Response measured:  Radioligand binding.
References:  32,51
α1A-AR antagonist silodosin (pA2 9.32) blocked norepinephrine-induced contraction with highest potency, indicationg that α1A-AR mediates norepinephrine-induced contraction of mouse ureter.
Species:  Mouse
Tissue:  Isolated ureteral preparations.
Response measured:  Contraction.
References:  41
Activation of α1A-AR increases cardiomyocyte shortening primarily via a phospholipase A2-dependent, Rho kinase-dependent increase in myofilament Ca2+ sensitivity which is potentiated by propofol via a PKC-dependent pathway and an increase in Na+ - H+ exchange activity.
Species:  Rat
Tissue:  Cardiomyocytes.
Response measured:  Contraction.
References:  19
α1A- and α1B-AR mediated seminal vesicle contractile responses. alpha1B- and alpha1D-adrenoceptor transcripts were both upregulated with surgical and chemical castration, suggesting a negative modulation by androgens.
Species:  Rat
Tissue:  Seminal vesicles.
Response measured:  Receptor transcription, contraction.
References:  52
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:  21
Increased levels of snapin and TRPC6.
Species:  Mouse
Tissue:  Heart muscle.
Response measured:  Increased systolic contractile function.
References:  56
Upregulation of connective tissue growth factor (CTGF).
Species:  Mouse
Tissue:  Heart muscle.
Response measured:  Development of a fibrotic heart phenotype post-myocardial infarction.
References:  14
NOS inhibition by L-NNA abolishes cardioprotective effects of α1A-adrenoceptor overexpression.
Species:  Rat
Tissue:  Heart.
Response measured:  Increased infarct size.
References:  104
Physiological Functions Click here for help
Contraction of stromal and capsular smooth muscle to control urethral resistance.
Species:  Human
Tissue:  Prostate.
References:  29
Contraction of urethral smooth muscle.
Species:  Human
Tissue:  Urethra.
References:  86
Stimulation of myocyte hypertrophy.
Species:  Rat
Tissue:  Myocardium.
References:  40
Contraction of skeletal muscle resistance arteries.
Species:  Human
Tissue:  Vasculature.
References:  36
Inhibition of outward current via the acid-sensitive potassium channel TASK-1 by α1A-AR.
Species:  Rat
Tissue:  Heart.
References:  67
Decreased α1A-AR but not α1B or α1D-AR mRNA in renal tissue during aging.
Species:  Rat
Tissue:  Kidney.
References:  45
Controls contraction of right gastroepiploic artery.
Species:  Human
Tissue:  Artery.
References:  26
Orthostatic hypotensive effect of antipsychotic drugs is mediated by α1A-AR.
Species:  Rat
Tissue:  Mesenteric arteries.
References:  58
Predominant involvement of α1A-AR in the contractile responses in human subcutaneous arteries.
Species:  Human
Tissue:  Subcutaneous arteries.
References:  35
Activation of sarcolemmal Na+-H+ exchanger.
Species:  Rat
Tissue:  Ventricular myocytes.
References:  83
Estrogen down-regulates α1A-AR expression in the urethral smooth muscle of female rats, suggesting a possible molecular mechanism through which estrogen affects urinary continence.
Species:  Rat
Tissue:  Intact urethra and isolated urethral smooth muscle cells.
References:  4
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:  76
Facilitates GABA release in the basolateral nucleus of the amygdala to mediate antiepileptic properties of norepinephrine.
Species:  Rat
Tissue:  Brain.
References:  3
Physiological Consequences of Altering Gene Expression Click here for help
Mice with systemic constitively active mutation (CAM) have increased synaptic plasticity, congition and longevity.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene over-expression.
References:  12
Cardiac specific overexpression of α1A-AR enhances cardiac contractility.
Species:  Mouse
Tissue:  Heart.
Technique:  Transgenesis.
References:  46
Hypotension and a decreased pressor response to phenylephrine are observed in α1A-AR knockout mice.
Species:  Mouse
Tissue:  In vivo.
Technique:  Transgenesis.
References:  70
Cardiac hypertrophy: mice with systemic constitively active mutation (CAM) secrete IL-6 and regulate cardiac hypertrophy through this pathway. Co-activation of both α1A- and α1B-ARs inhibits development of hypertrophy.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  62
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:  23
Mice with systemic constitively active mutation (CAM) are preconditioned against ischemia through PKC mechanism.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  71
In knockout mice, α1A-AR can regulate ERK survival signaling pathway and decrease apoptosis in adult myocytes.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knockouts.
References:  31
Mice with receptor over-expression develop a hypercontractile inotropic phenotype: hypercontraction and high fractional shortening.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene over-expression.
References:  13
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:  1
Cardioprotection in rats with α1A-adrenoceptor overexpression phenocopy non-transgenic littermate control rats with second window of preconditioning that is mediated by iNOS activation.
Species:  Rat
Tissue:  Heart.
Technique:  Gene over-expression.
References:  104
Increased p-MEK and p-ERK in rats with α1A-adrenoceptor overexpression.
Species:  Rat
Tissue:  Heart.
Technique:  Gene over-expression.
References:  104
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.
References:  85
Peroxynitrite generated through septic shock (bacterial infection) can inhibit maximum binding and signal transduction (intracellular calcium) of the α1A- and α1D-AR. This may be due to modification of these receptor subtypes by peroxynitrite and represents a possible mechanism contributing to systemic hypotension in sepsis.
Species:  Human
Tissue:  CHO cells transfected with the human α1A-, α1B- and α1D-ARs.
Technique:  Ligand binding and measurement of intracellular calcium.
References:  85
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
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0002972 abnormal cardiac muscle contractility PMID: 14519431 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0000304 abnormal cardiac stroke volume PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0001544 abnormal cardiovascular system physiology PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0002332 abnormal exercise endurance PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0005406 abnormal heart size PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0004215 abnormal myocardial fiber physiology PMID: 14519431 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0006138 congestive heart failure PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0003393 decreased cardiac output PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0005333 decreased heart rate PMID: 12782680 
Adra1atm1Pcs Adra1atm1Pcs/Adra1atm1Pcs
involves: 129X1/SvJ * FVB/N		 MGI:104773  MP:0003929 decreased heart rate variability PMID: 12093905 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0002834 decreased heart weight PMID: 12782680 
Adra1atm1Pcs Adra1atm1Pcs/Adra1atm1Pcs
involves: 129X1/SvJ * FVB/N		 MGI:104773  MP:0003026 decreased vasoconstriction PMID: 12093905 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0003068 enlarged kidney PMID: 12782680 
Adra1atm1Pcs Adra1atm1Pcs/Adra1atm1Pcs
involves: 129X1/SvJ * FVB/N		 MGI:104773  MP:0001596 hypotension PMID: 12093905 
Adra1a+|Adra1atm1Pcs Adra1atm1Pcs/Adra1a+
involves: 129X1/SvJ * FVB/N		 MGI:104773  MP:0001596 hypotension PMID: 12093905 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0005599 increased cardiac muscle contractility PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0003823 increased left ventricular developed pressure PMID: 14519431 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0004485 increased response of heart to induced stress PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0002188 small heart PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
B6.129-Adra1b Adra1a		 MGI:104773  MGI:104774  MP:0002188 small heart PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * FVB/N		 MGI:104773  MGI:104774  MP:0004565 small myocardial fiber PMID: 12782680 
Adra1atm1Pcs|Adra1btm1Cta Adra1atm1Pcs/Adra1atm1Pcs,Adra1btm1Cta/Adra1btm1Cta
B6.129-Adra1b Adra1a		 MGI:104773  MGI:104774  MP:0004565 small myocardial fiber PMID: 12782680 
Gene Expression and Pathophysiology Click here for help
Downregulation of α1A-AR but not α1B-AR
Tissue or cell type: 
Pathophysiology:  Dilated cardiomyopathy
Species:  Human
Technique: 
References:  80
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Arg492Cys polymorphism is not associated with hypertension in Caucasian and African-Americans, but with ethnicity.
Amino acids:  492
References:  97
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Arg347Cys polymorphism is associated with hypertension (diastolic blood pressure) in Brazilian population,
References:  18
Type:  Missense mutation
Species:  Human
Description:  The 347Arg and 2547G alleles are associated with hypertension in northern Han Chinese population.
Amino acid change:  R347C
Nucleotide change:  1475C>T
References:  22
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Arg347Cys polymorphism is associated with diastolic blood pressure response to short-term irbesartan (AT1 antagonist) treatment in Chinese hypertensive subjects.
References:  37

References

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