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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 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

Show »

1. Amirahmadi F, Turnbull L, Du XJ, Graham RM, Woodcock EA. (2008) Heightened alpha1A-adrenergic receptor activity suppresses ischaemia/reperfusion-induced Ins(1,4,5)P3 generation in the mouse heart: a comparison with ischaemic preconditioning. Clin Sci, 114 (2): 157-64. [PMID:17696883]

2. Amirak E, Fuller SJ, Sugden PH, Clerk A. (2013) p90 ribosomal S6 kinases play a significant role in early gene regulation in the cardiomyocyte response to G(q)-protein-coupled receptor stimuli, endothelin-1 and α(1)-adrenergic receptor agonists. Biochem J, 450 (2): 351-63. [PMID:23215897]

3. Aroniadou-Anderjaska V, Qashu F, Braga MF. (2007) Mechanisms regulating GABAergic inhibitory transmission in the basolateral amygdala: implications for epilepsy and anxiety disorders. Amino Acids, 32 (3): 305-15. [PMID:17048126]

4. Banie L, Lin G, Ning H, Wang G, Lue TF, Lin CS. (2008) Effects of estrogen, raloxifene and levormeloxifene on alpha1A-adrenergic receptor expression. J Urol, 180 (5): 2241-6. [PMID:18804812]

5. Blue DR, Daniels DV, Gever JR, Jett MF, O'Yang C, Tang HM, Williams TJ, Ford AP. (2004) Pharmacological characteristics of Ro 115-1240, a selective alpha1A/1L-adrenoceptor partial agonist: a potential therapy for stress urinary incontinence. BJU Int, 93 (1): 162-70. [PMID:14678390]

6. Bolaños B, Mitchell TG. (1989) Phagocytosis and killing of Cryptococcus neoformans by rat alveolar macrophages in the absence of serum. J Leukoc Biol, 46 (6): 521-8. [PMID:2681492]

7. Carroll WA, Sippy KB, Esbenshade TA, Buckner SA, Hancock AA, Meyer MD. (2001) Two novel and potent 3-[(o-methoxyphenyl)piperazinylethyl]-5-phenylthien. Bioorg Med Chem Lett, 11 (9): 1119-21. [PMID:11354357]

8. Chang DJ, Chang TK, Yamanishi SS, Salazar FH, Kosaka AH, Khare R, Bhakta S, Jasper JR, Shieh IS, Lesnick JD et al.. (1998) Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett, 422 (2): 279-83. [PMID:9490024]

9. da Silva Junior ED, Sato M, Merlin J, Broxton N, Hutchinson DS, Ventura S, Evans BA, Summers RJ. (2017) Factors influencing biased agonism in recombinant cells expressing the human α1A -adrenoceptor. Br J Pharmacol, 174 (14): 2318-2333. [PMID:28444738]

10. Daniels DV, Gever JR, Jasper JR, Kava MS, Lesnick JD, Meloy TD, Stepan G, Williams TJ, Clarke DE, Chang DJ et al.. (1999) Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies. Eur J Pharmacol, 370 (3): 337-43. [PMID:10334511]

11. Day HE, Campeau S, Watson Jr SJ, Akil H. (1997) Distribution of alpha 1a-, alpha 1b- and alpha 1d-adrenergic receptor mRNA in the rat brain and spinal cord. J Chem Neuroanat, 13 (2): 115-39. [PMID:9285356]

12. Doze VA, Papay RS, Goldenstein BL, Gupta MK, Collette KM, Nelson BW, Lyons MJ, Davis BA, Luger EJ, Wood SG et al.. (2011) Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity. Mol Pharmacol, 80 (4): 747-58. [PMID:21791575]

13. Du XJ, Fang L, Gao XM, Kiriazis H, Feng X, Hotchkin E, Finch AM, Chaulet H, Graham RM. (2004) Genetic enhancement of ventricular contractility protects against pressure-overload-induced cardiac dysfunction. J Mol Cell Cardiol, 37 (5): 979-87. [PMID:15522275]

14. Du XJ, Gao XM, Kiriazis H, Moore XL, Ming Z, Su Y, Finch AM, Hannan RA, Dart AM, Graham RM. (2006) Transgenic alpha1A-adrenergic activation limits post-infarct ventricular remodeling and dysfunction and improves survival. Cardiovasc Res, 71 (4): 735-43. [PMID:16859660]

15. Evans BA, Broxton N, Merlin J, Sato M, Hutchinson DS, Christopoulos A, Summers RJ. (2011) Quantification of functional selectivity at the human α(1A)-adrenoceptor. Mol Pharmacol, 79 (2): 298-307. [PMID:20978120]

16. Ford AP, Arredondo NF, Blue Jr DR, Bonhaus DW, Jasper J, Kava MS, Lesnick J, Pfister JR, Shieh IA, Vimont RL et al.. (1996) RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective alpha 1A-adrenoceptor antagonist, displays low affinity for functional alpha 1-adrenoceptors in human prostate: implications for adrenoceptor classification. Mol Pharmacol, 49 (2): 209-15. [PMID:8632751]

17. Ford AP, Daniels DV, Chang DJ, Gever JR, Jasper JR, Lesnick JD, Clarke DE. (1997) Pharmacological pleiotropism of the human recombinant alpha1A-adrenoceptor: implications for alpha1-adrenoceptor classification. Br J Pharmacol, 121 (6): 1127-35. [PMID:9249248]

18. Freitas SR, Pereira AC, Floriano MS, Mill JG, Krieger JE. (2008) Association of alpha1a-adrenergic receptor polymorphism and blood pressure phenotypes in the Brazilian population. BMC Cardiovasc Disord, 8: 40. [PMID:19105822]

19. Gable BD, Shiga T, Murray PA, Damron DS. (2005) Propofol increases contractility during alpha1a-adrenoreceptor activation in adult rat cardiomyocytes. Anesthesiology, 103 (2): 335-43. [PMID:16052116]

20. Giardinà D, Crucianelli M, Romanelli R, Leonardi A, Poggesi E, Melchiorre C. (1996) Synthesis and biological profile of the enantiomers of [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin- 1-yl]furan-2-ylmethanone (cyclazosin), a potent competitive alpha 1B- adrenoceptor antagonist. J Med Chem, 39 (23): 4602-7. [PMID:8917649]

21. Gonzalez-Cabrera PJ, Shi T, Yun J, McCune DF, Rorabaugh BR, Perez DM. (2004) Differential regulation of the cell cycle by alpha1-adrenergic receptor subtypes. Endocrinology, 145 (11): 5157-67. [PMID:15297446]

22. Gu D, Ge D, Snieder H, He J, Chen S, Huang J, Li B, Chen R, Qiang B. (2006) Association of alpha1A adrenergic receptor gene variants on chromosome 8p21 with human stage 2 hypertension. J Hypertens, 24 (6): 1049-56. [PMID:16685204]

23. Gupta MK, Papay RS, Jurgens CW, Gaivin RJ, Shi T, Doze VA, Perez DM. (2009) alpha1-Adrenergic receptors regulate neurogenesis and gliogenesis. Mol Pharmacol, 76 (2): 314-26. [PMID:19487244]

24. Hague C, Bernstein LS, Ramineni S, Chen Z, Minneman KP, Hepler JR. (2005) Selective inhibition of alpha1A-adrenergic receptor signaling by RGS2 association with the receptor third intracellular loop. J Biol Chem, 280 (29): 27289-95. [PMID:15917235]

25. Hague C, Chen Z, Uberti M, Minneman KP. (2003) Alpha(1)-adrenergic receptor subtypes: non-identical triplets with different dancing partners?. Life Sci, 74 (4): 411-8. [PMID:14609720]

26. Han JL, Zhang YY, Lü ZZ, Mao JM, Chen MZ, Han QD. (2003) Functional alpha1-adrenergic receptor subtypes in human right gastroepiploic artery. Acta Pharmacol Sin, 24 (4): 327-31. [PMID:12676072]

27. Hancock AA, Buckner SA, Brune ME, Katwala S, Milicic I, Ireland LM, Morse PA, Knepper SM, Meyer MD,Chapple CR et al.. (1998) Pharmacological characterization of A-131701, a novel R 1 -adrenoceptor antagonist selective for R 1A - and R 1D - compared to R 1B -adrenoceptors. Drug Development Research, 44: 140-162.

28. Hieble JP. (2000) Adrenoceptor subclassification: an approach to improved cardiovascular therapeutics. Pharm Acta Helv, 74 (2-3): 163-71. [PMID:10812954]

29. Hieble JP, Ruffolo Jr RR. (1997) Recent advances in the identification of alpha1- and alpha2-adrenoceptor subtypes: therapeutic implications. Expert Opin Investig Drugs, 6 (4): 367-87. [PMID:15989605]

30. Horie K, Obika K, Foglar R, Tsujimoto G. (1995) Selectivity of the imidazoline alpha-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned alpha 1-adrenoceptor subtypes. Br J Pharmacol, 116 (1): 1611-8. [PMID:8564227]

31. Huang Y, Wright CD, Merkwan CL, Baye NL, Liang Q, Simpson PC, O'Connell TD. (2007) An alpha1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. Circulation, 115 (6): 763-72. [PMID:17283256]

32. Hwa J, Graham RM, Perez DM. (1995) Identification of critical determinants of alpha 1-adrenergic receptor subtype selective agonist binding. J Biol Chem, 270 (39): 23189-95. [PMID:7559466]

33. Hwa J, Graham RM, Perez DM. (1996) Chimeras of alpha1-adrenergic receptor subtypes identify critical residues that modulate active state isomerization. J Biol Chem, 271 (14): 7956-64. [PMID:8626475]

34. Hwa J, Perez DM. (1996) The unique nature of the serine interactions for alpha 1-adrenergic receptor agonist binding and activation. J Biol Chem, 271 (11): 6322-7. [PMID:8626427]

35. Jarajapu YP, Johnston F, Berry C, Renwick A, McGrath JC, MacDonald A, Hillier C. (2001) Functional characterization of alpha1-adrenoceptor subtypes in human subcutaneous resistance arteries. J Pharmacol Exp Ther, 299 (2): 729-34. [PMID:11602687]

36. Jarajapu YP, McGrath JC, Hillier C, MacDonald A. (2003) The alpha 1-adrenoceptor profile in human skeletal muscle resistance arteries in critical limb ischaemia. Cardiovasc Res, 57 (2): 554-62. [PMID:12566128]

37. Jiang S, Mao G, Zhang S, Hong X, Tang G, Li Z, Liu X, Zhang Y, Wang B, Xu X et al.. (2005) Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects. Clin Pharmacol Ther, 78 (3): 239-48. [PMID:16153395]

38. Kawanabe Y, Hashimoto N, Masaki T. (2004) Characterization of G proteins involved in activation of nonselective cation channels and arachidonic acid release by norepinephrine/alpha1A-adrenergic receptors. Am J Physiol, Cell Physiol, 286 (3): C596-600. [PMID:14761886]

39. Knepper SM, Buckner SA, Brune ME, DeBernardis JF, Meyer MD, Hancock AA. (1995) A-61603, a potent alpha 1-adrenergic receptor agonist, selective for the alpha 1A receptor subtype. J Pharmacol Exp Ther, 274 (1): 97-103. [PMID:7616455]

40. Knowlton KU, Michel MC, Itani M, Shubeita HE, Ishihara K, Brown JH, Chien KR. (1993) The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy. J Biol Chem, 268 (21): 15374-80. [PMID:8393439]

41. Kobayashi S, Tomiyama Y, Hoyano Y, Yamazaki Y, Kusama H, Itoh Y, Kubota Y, Kohri K. (2009) Gene expressions and mechanical functions of α1-adrenoceptor subtypes in mouse ureter. World J Urol, 27 (6): 775-80. [PMID:19259685]

42. Kobori N, Hu B, Dash PK. (2011) Altered adrenergic receptor signaling following traumatic brain injury contributes to working memory dysfunction. Neuroscience, 172: 293-302. [PMID:20974230]

43. Lee D, Robeva A, Chen Z, Minneman KP. (2003) Mutational uncoupling of alpha1A-adrenergic receptors from G proteins also uncouples mitogenic and transcriptional responses in PC12 cells. J Pharmacol Exp Ther, 306 (2): 471-7. [PMID:12724349]

44. Leonardi A, Hieble JP, Guarneri L, Naselsky DP, Poggesi E, Sironi G, Sulpizio AC, Testa R. (1997) Pharmacological characterization of the uroselective alpha-1 antagonist Rec 15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity, part I. J Pharmacol Exp Ther, 281 (3): 1272-83. [PMID:9190863]

45. Li YF, Cao XJ, Bai XY, Lin SP, Shi ST. (2010) Change of expression of renal alpha1-adrenergic receptor and angiotensin II receptor subtypes with aging in rats. Aging Clin Exp Res, 22 (2): 123-8. [PMID:20440098]

46. Lin F, Owens WA, Chen S, Stevens ME, Kesteven S, Arthur JF, Woodcock EA, Feneley MP, Graham RM. (2001) Targeted alpha(1A)-adrenergic receptor overexpression induces enhanced cardiac contractility but not hypertrophy. Circ Res, 89 (4): 343-50. [PMID:11509451]

47. Liu CM, Lo YC, Wu BN, Wu WJ, Chou YH, Huang CH, An LM, Chen IJ. (2007) cGMP-enhancing- and alpha1A/alpha1D-adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacy. Prostate, 67 (13): 1397-410. [PMID:17639498]

48. Liu F, He K, Yang X, Xu N, Liang Z, Xu M, Zhao X, Han Q, Zhang Y. (2011) α1A-adrenergic receptor induces activation of extracellular signal-regulated kinase 1/2 through endocytic pathway. PLoS ONE, 6 (6): e21520. [PMID:21738688]

49. Mackenzie JF, Daly CJ, Pediani JD, McGrath JC. (2000) Quantitative imaging in live human cells reveals intracellular alpha(1)-adrenoceptor ligand-binding sites. J Pharmacol Exp Ther, 294 (2): 434-43. [PMID:10900216]

50. Maïga A, Merlin J, Marcon E, Rouget C, Larregola M, Gilquin B, Fruchart-Gaillard C, Lajeunesse E, Marchetti C, Lorphelin A et al.. (2013) Orthosteric binding of ρ-Da1a, a natural peptide of snake venom interacting selectively with the α1A-adrenoceptor. PLoS ONE, 8 (7): e68841. [PMID:23935897]

51. McCune D, Gaivin R, Rorabaugh B, Perez D. (2004) Bulk is a determinant of oxymetazoline affinity for the alpha1A-adrenergic receptor. Recept Channels, 10 (3-4): 109-16. [PMID:15512845]

52. Mendes FR, Hamamura M, Queiróz DB, Porto CS, Avellar MC. (2004) Effects of androgen manipulation on alpha1-adrenoceptor subtypes in the rat seminal vesicle. Life Sci, 75 (12): 1449-63. [PMID:15240180]

53. Meyer MD, Altenbach RJ, Basha FZ, Carroll WA, Drizin I, Elmore SW, Ehrlich PP, Lebold SA, Tietje K, Sippy KB et al.. (1997) Synthesis and pharmacological characterization of 3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b-hexahydro-1H-benz[e] isoindol-2-yl)ethyl]pyrido-[3',4':4,5]thieno[3,2-d]pyrimidine-2,4 (1H,3H)-dione (A-131701): a uroselective alpha 1A adrenoceptor antagonist for the symptomatic treatment of benign prostatic hyperplasia. J Med Chem, 40 (20): 3141-3. [PMID:9379432]

54. Michelotti GA, Price DT, Schwinn DA. (2000) Alpha 1-adrenergic receptor regulation: basic science and clinical implications. Pharmacol Ther, 88 (3): 281-309. [PMID:11337028]

55. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther, 303 (2): 791-804. [PMID:12388666]

56. Mohl MC, Iismaa SE, Xiao XH, Friedrich O, Wagner S, Nikolova-Krstevski V, Wu J, Yu ZY, Feneley M, Fatkin D et al.. (2011) Regulation of murine cardiac contractility by activation of α(1A)-adrenergic receptor-operated Ca(2+) entry. Cardiovasc Res, 91 (2): 310-9. [PMID:21546445]

57. Morris DP, Price RR, Smith MP, Lei B, Schwinn DA. (2004) Cellular trafficking of human alpha1a-adrenergic receptors is continuous and primarily agonist-independent. Mol Pharmacol, 66 (4): 843-54. [PMID:15258254]

58. Nourian Z, Mow T, Muftic D, Burek S, Pedersen ML, Matz J, Mulvany MJ. (2008) Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of alpha1-adrenoceptor function. Psychopharmacology (Berl.), 199 (1): 15-27. [PMID:18542932]

59. Obika K, Shibata K, Horie K, Foglar R, Kimura K, Tsujimoto G. (1995) NS-49, a novel alpha 1a-adrenoceptor-selective agonist characterization using recombinant human alpha 1-adrenoceptors. Eur J Pharmacol, 291 (3): 327-34. [PMID:8719417]

60. Ohmura T, Oshita M, Kigoshi S, Muramatsu I. (1992) Identification of alpha 1-adrenoceptor subtypes in the rat vas deferens: binding and functional studies. Br J Pharmacol, 107 (3): 697-704. [PMID:1361871]

61. Papay R, Gaivin R, Jha A, McCune DF, McGrath JC, Rodrigo MC, Simpson PC, Doze VA, Perez DM. (2006) Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors. J Comp Neurol, 497 (2): 209-22. [PMID:16705673]

62. Papay RS, Shi T, Piascik MT, Naga Prasad SV, Perez DM. (2013) α₁A-adrenergic receptors regulate cardiac hypertrophy in vivo through interleukin-6 secretion. Mol Pharmacol, 83 (5): 939-48. [PMID:23404509]

63. Parmentier JH, Gandhi GK, Wiggins MT, Saeed AE, Bourgoin SG, Malik KU. (2004) Protein kinase Czeta regulates phospholipase D activity in rat-1 fibroblasts expressing the alpha1A adrenergic receptor. BMC Cell Biol, 5: 4. [PMID:14736339]

64. Price DT, Lefkowitz RJ, Caron MG, Berkowitz D, Schwinn DA. (1994) Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol, 45 (2): 171-5. [PMID:8114668]

65. Proudman RGW, Baker JG. (2021) The selectivity of α-adrenoceptor agonists for the human α1A, α1B, and α1D-adrenoceptors. Pharmacol Res Perspect, 9 (4): e00799. [PMID:34355529]

66. Proudman RGW, Pupo AS, Baker JG. (2020) The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors. Pharmacol Res Perspect, 8 (4): e00602. [PMID:32608144]

67. Putzke C, Wemhöner K, Sachse FB, Rinné S, Schlichthörl G, Li XT, Jaé L, Eckhardt I, Wischmeyer E, Wulf H et al.. (2007) The acid-sensitive potassium channel TASK-1 in rat cardiac muscle. Cardiovasc Res, 75 (1): 59-68. [PMID:17389142]

68. Queiróz DB, Mendes FR, Porto CS, Avellar MC. (2002) Alpha1-adrenoceptor subtypes in rat epididymis and the effects of sexual maturation. Biol Reprod, 66 (2): 508-15. [PMID:11804969]

69. Quinton L, Girard E, Maiga A, Rekik M, Lluel P, Masuyer G, Larregola M, Marquer C, Ciolek J, Magnin T et al.. (2010) Isolation and pharmacological characterization of AdTx1, a natural peptide displaying specific insurmountable antagonism of the alpha1A-adrenoceptor. Br J Pharmacol, 159 (2): 316-25. [PMID:20015090]

70. Rokosh DG, Simpson PC. (2002) Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc Natl Acad Sci USA, 99 (14): 9474-9. [PMID:12093905]

71. Rorabaugh BR, Ross SA, Gaivin RJ, Papay RS, McCune DF, Simpson PC, Perez DM. (2005) alpha1A- but not alpha1B-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism. Cardiovasc Res, 65 (2): 436-45. [PMID:15639483]

72. Saeed AE, Parmentier JH, Malik KU. (2004) Activation of alpha1A-adrenergic receptor promotes differentiation of rat-1 fibroblasts to a smooth muscle-like phenotype. BMC Cell Biol, 5 (1): 47. [PMID:15603588]

73. Salomonsson M, Oker M, Kim S, Zhang H, Faber JE, Arendshorst WJ. (2001) Alpha1-adrenoceptor subtypes on rat afferent arterioles assessed by radioligand binding and RT-PCR. Am J Physiol Renal Physiol, 281 (1): F172-8. [PMID:11399658]

74. Santana N, Mengod G, Artigas F. (2013) Expression of α(1)-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT(2A) receptors. Int J Neuropsychopharmacol, 16 (5): 1139-51. [PMID:23195622]

75. Saussy Jr DL, Goetz AS, Queen KL, King HK, Lutz MW, Rimele TJ. (1996) Structure activity relationships of a series of buspirone analogs at alpha-1 adrenoceptors: further evidence that rat aorta alpha-1 adrenoceptors are of the alpha-1D-subtype. J Pharmacol Exp Ther, 278 (1): 136-44. [PMID:8764344]

76. Schilit S, Benzeroual KE. (2009) Silodosin: a selective alpha1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia. Clin Ther, 31 (11): 2489-502. [PMID:20109995]

77. Schwinn DA, Johnston GI, Page SO, Mosley MJ, Wilson KH, Worman NP, Campbell S, Fidock MD, Furness LM, Parry-Smith DJ et al.. (1995) Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther, 272 (1): 134-42. [PMID:7815325]

78. Sharpe IA, Thomas L, Loughnan M, Motin L, Palant E, Croker DE, Alewood D, Chen S, Graham RM, Alewood PF et al.. (2003) Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIA. J Biol Chem, 278 (36): 34451-7. [PMID:12824165]

79. Shi T, Duan ZH, Papay R, Pluskota E, Gaivin RJ, de la Motte CA, Plow EF, Perez DM. (2006) Novel alpha1-adrenergic receptor signaling pathways: secreted factors and interactions with the extracellular matrix. Mol Pharmacol, 70 (1): 129-42. [PMID:16617165]

80. Shi T, Moravec CS, Perez DM. (2013) Novel proteins associated with human dilated cardiomyopathy: selective reduction in α1A-adrenergic receptors and increased desensitization proteins. J Recept Signal Transduct Res, 33 (2): 96-106. [PMID:23384050]

81. Shi T, Papay RS, Perez DM. (2012) α(1A)-adrenergic receptor differentially regulates STAT3 phosphorylation through PKCϵ and PKCδ in myocytes. J Recept Signal Transduct Res, 32 (2): 76-86. [PMID:22268811]

82. Shibata K, Foglar R, Horie K, Obika K, Sakamoto A, Ogawa S, Tsujimoto G. (1995) KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. Mol Pharmacol, 48 (2): 250-8. [PMID:7651358]

83. Snabaitis AK, Yokoyama H, Avkiran M. (2000) Roles of mitogen-activated protein kinases and protein kinase C in alpha(1A)-adrenoceptor-mediated stimulation of the sarcolemmal Na(+)-H(+) exchanger. Circ Res, 86 (2): 214-20. [PMID:10666418]

84. Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. (2005) Alpha1-adrenoreceptor in human hippocampus: binding and receptor subtype mRNA expression. Brain Res Mol Brain Res, 139 (2): 367-71. [PMID:16039007]

85. Takakura K, Taniguchi T, Muramatsu I, Takeuchi K, Fukuda S. (2002) Modification of alpha1 -adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis. Crit Care Med, 30 (4): 894-9. [PMID:11940765]

86. Taniguchi N, Hamada K, Ogasawara T, Ukai Y, Yoshikuni Y, Kimura K. (1996) NS-49, an alpha 1A-adrenoceptor agonist, selectively increases intraurethral pressure in dogs. Eur J Pharmacol, 318 (1): 117-22. [PMID:9007522]

87. Taniguchi T, Inagaki R, Murata S, Akiba I, Muramatsu I. (1999) Microphysiometric analysis of human alpha1a-adrenoceptor expressed in Chinese hamster ovary cells. Br J Pharmacol, 127 (4): 962-8. [PMID:10433504]

88. Tayebati SK, Bronzetti E, Morra Di Cella S, Mulatero P, Ricci A, Rossodivita I, Schena M, Schiavone D, Veglio F, Amenta F. (2000) In situ hybridization and immunocytochemistry of alpha1-adrenoceptors in human peripheral blood lymphocytes. J Auton Pharmacol, 20 (5-6): 305-12. [PMID:11350496]

89. Walden PD, Gerardi C, Lepor H. (1999) Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors in hyperplastic and non-hyperplastic human prostate. J Urol, 161 (2): 635-40. [PMID:9915474]

90. Waugh DJ, Gaivin RJ, Damron DS, Murray PA, Perez DM. (1999) Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation. J Pharmacol Exp Ther, 291 (3): 1164-71. [PMID:10565838]

91. Waugh DJ, Gaivin RJ, Zuscik MJ, Gonzalez-Cabrera P, Ross SA, Yun J, Perez DM. (2001) Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like antagonists. J Biol Chem, 276 (27): 25366-71. [PMID:11331292]

92. Wetzel JM, Miao SW, Forray C, Borden LA, Branchek TA, Gluchowski C. (1995) Discovery of alpha 1a-adrenergic receptor antagonists based on the L-type Ca2+ channel antagonist niguldipine. J Med Chem, 38 (10): 1579-81. [PMID:7752182]

93. Williams LM, He X, Vaid TM, Abdul-Ridha A, Whitehead AR, Gooley PR, Bathgate RAD, Williams SJ, Scott DJ. (2019) Diazepam is not a direct allosteric modulator of α1-adrenoceptors, but modulates receptor signaling by inhibiting phosphodiesterase-4. Pharmacol Res Perspect, 7 (1): e00455. [PMID:30619611]

94. Williams TJ, Blue DR, Daniels DV, Davis B, Elworthy T, Gever JR, Kava MS, Morgans D, Padilla F, Tassa S et al.. (1999) In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists. Br J Pharmacol, 127 (1): 252-8. [PMID:10369480]

95. Wright CD, Chen Q, Baye NL, Huang Y, Healy CL, Kasinathan S, O'Connell TD. (2008) Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes. Circ Res, 103 (9): 992-1000. [PMID:18802028]

96. Wright CD, Wu SC, Dahl EF, Sazama AJ, O'Connell TD. (2012) Nuclear localization drives α1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cell Signal, 24 (3): 794-802. [PMID:22120526]

97. Xie HG, Kim RB, Stein CM, Gainer JV, Brown NJ, Wood AJ. (1999) Alpha1A-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension. Pharmacogenetics, 9 (5): 651-6. [PMID:10591546]

98. Yan M, Sun J, Bird PI, Liu DL, Grigg M, Lim YL. (2001) Alpha1A- and alpha1B-adrenoceptors are the major subtypes in human saphenous vein. Life Sci, 68 (10): 1191-8. [PMID:11228103]

99. Yanase H, Wang X, Momota Y, Nimura T, Kawatani M. (2008) The involvement of urothelial alpha1A adrenergic receptor in controlling the micturition reflex. Biomed Res, 29 (5): 239-44. [PMID:18997438]

100. Yoshio R, Taniguchi T, Itoh H, Muramatsu I. (2001) Affinity of serotonin receptor antagonists and agonists to recombinant and native alpha1-adrenoceptor subtypes. Jpn J Pharmacol, 86 (2): 189-95. [PMID:11459121]

101. Zhang H, Faber JE. (2001) Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different alpha1-adrenoceptor subtypes. Circ Res, 89 (9): 815-22. [PMID:11679412]

102. Zhang Y, Kolli T, Hivley R, Jaber L, Zhao FI, Yan J, Herness S. (2010) Characterization of the expression pattern of adrenergic receptors in rat taste buds. Neuroscience, 169 (3): 1421-37. [PMID:20478367]

103. Zhao MM, Hwa J, Perez DM. (1996) Identification of critical extracellular loop residues involved in alpha 1-adrenergic receptor subtype-selective antagonist binding. Mol Pharmacol, 50 (5): 1118-26. [PMID:8913343]

104. Zhao X, Park J, Ho D, Gao S, Yan L, Ge H, Iismaa S, Lin L, Tian B, Vatner DE et al.. (2012) Cardiomyocyte overexpression of the α1A-adrenergic receptor in the rat phenocopies second but not first window preconditioning. Am J Physiol Heart Circ Physiol, 302 (8): H1614-24. [PMID:22307672]

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