Alpha-1A adrenergic receptor

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The alpha-1A adrenergic receptor (α_1A adrenoreceptor), also known as ADRA1A, formerly known also as the alpha-1C adrenergic receptor,^[5] is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.^[6] There is no longer a subtype α_1C receptor. At one time, there was a subtype known as α_1C, but it was found to be identical to the previously discovered α_1A receptor subtype. To avoid confusion, the naming convention was continued with the letter D.

ADRA1A

Identifiers

Aliases

ADRA1A, ADRA1C, ADRA1L1, ALPHA1AAR, adrenoceptor alpha 1A

External IDs

OMIM: 104221; MGI: 104773; HomoloGene: 68078; GeneCards: ADRA1A; OMA:ADRA1A - orthologs

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8p21.2	Start	26,748,150 bp^[1]
Band	8p21.2	End	26,867,278 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 14 (mouse)^[2]

Band	14\|14 D1	Start	66,872,700 bp^[2]
Band	14\|14 D1	End	67,008,617 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

right lobe of liver

buccal mucosa cell

right lung

apex of heart

left ventricle

right ventricle

testicle

tail of epididymis

upper lobe of left lung

spleen

Top expressed in

right kidney

superior frontal gyrus

primary visual cortex

dentate gyrus of hippocampal formation granule cell

muscle of thigh

brown adipose tissue

supraoptic nucleus

cerebellar cortex

ventricular zone

neural tube

More reference expression data

BioGPS

More reference expression data

Gene ontology
Molecular function	signal transducer activity adrenergic receptor activity protein heterodimerization activity G protein-coupled receptor activity alpha1-adrenergic receptor activity protein binding
Cellular component	T-tubule nuclear membrane integral component of membrane nucleus integral component of plasma membrane membrane Z discdkac plasma membrane cytoplasm caveola dopaminergic synapse glutamatergic synapse GABA-ergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane
Biological process	positive regulation of cardiac muscle contraction negative regulation of cell population proliferation response to hormone norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure positive regulation of MAPK cascade intracellular signal transduction positive regulation of ERK1 and ERK2 cascade signal transduction organ growth cell-cell signaling positive regulation of smooth muscle contraction activation of phospholipase C activity pilomotor reflex regulation of vasoconstriction positive regulation of heart rate positive regulation of synaptic transmission, GABAergic positive regulation of systemic arterial blood pressure G protein-coupled receptor signaling pathway urination calcium ion transport into cytosol positive regulation of action potential positive regulation of the force of heart contraction by epinephrine-norepinephrine apoptotic process smooth muscle contraction phospholipase C-activating G protein-coupled receptor signaling pathway adenylate cyclase-activating adrenergic receptor signaling pathway human ageing regulation of cardiac muscle contraction positive regulation of heart rate by epinephrine-norepinephrine positive regulation of protein kinase C signaling negative regulation of Rho protein signal transduction regulation of muscle contraction adult heart development negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure positive regulation of cytosolic calcium ion concentration positive regulation of vasoconstriction negative regulation of autophagy positive regulation of cardiac muscle hypertrophy positive regulation of non-membrane spanning protein tyrosine kinase activity cell growth involved in cardiac muscle cell development regulation of synaptic vesicle exocytosis adenylate cyclase-modulating G protein-coupled receptor signaling pathway neuron-glial cell signaling
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


148


11549

Ensembl


ENSG00000120907


ENSMUSG00000045875

UniProt


P35348


P97718

RefSeq (mRNA)

NM_000680 NM_033302 NM_033303 NM_033304 NM_001322502
NM_001322503 NM_001322504


NM_001271759 NM_001271760 NM_001271761 NM_013461

RefSeq (protein)

NP_000671 NP_001309431 NP_001309432 NP_001309433 NP_150645
NP_150646 NP_150647


NP_001258688 NP_001258689 NP_001258690 NP_038489

Location (UCSC)

Chr 8: 26.75 – 26.87 Mb

Chr 14: 66.87 – 67.01 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

There are 3 alpha-1 adrenergic receptor subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins. Different subtypes show different patterns of activation. The majority of alpha-1 receptors are directed toward the function of epinephrine, a hormone that has to do with the fight-or-flight response.

This gene encodes the alpha-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties.^[6]

6-(5-fluoro-2-pyrimidin-5-yl-phenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole: EC₅₀ = 1nM, E_max = 65%; good selectivity over α1B, α1D and α2A subtypes^[7]
further partial agonistic imidazole compounds^[8]^[9]
A-61603^[10]
Metaraminol

Tamsulosin: for treatment of benign prostatic hyperplasia
Silodosin: for treatment of benign prostatic hyperplasia
Doxazosin: for treatment of benign prostatic hyperplasia and/or Hypertension
Risperidone: used to treat schizophrenia and bipolar disorder
WB-4101
Ziprasidone
Nicergoline
Most tricyclic antidepressants

Role in neural circuits

edit

α1A-adrenergic receptor subtypes increase inhibition at dendrodendritic synapses, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors.^[11]

Adrenergic receptor

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000120907 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000045875 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Langer SZ (1998). "Nomenclature and state of the art on alpha1-adrenoceptors". Eur. Urol. 33 (Suppl 2): 2–6. doi:10.1159/000052227. PMID 9556189.
^ ^a ^b "Entrez Gene: ADRA1A adrenergic, alpha-1A-, receptor".
^ Roberts LR, Fish PV, Ian Storer R, Whitlock GA (April 2009). "6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha(1A) adrenoceptor partial agonists". Bioorg. Med. Chem. Lett. 19 (11): 3113–7. doi:10.1016/j.bmcl.2009.03.166. PMID 19414260.
^ Whitlock GA, Brennan PE, Roberts LR, Stobie A (April 2009). "Potent and selective alpha(1A) adrenoceptor partial agonists-Novel imidazole frameworks". Bioorg. Med. Chem. Lett. 19 (11): 3118–21. doi:10.1016/j.bmcl.2009.03.162. PMID 19394220.
^ Roberts LR, Bryans J, Conlon K, McMurray G, Stobie A, Whitlock GA (December 2008). "Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists". Bioorg. Med. Chem. Lett. 18 (24): 6437–40. doi:10.1016/j.bmcl.2008.10.066. PMID 18980842.
^ 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.
^ Zimnik NC, Treadway T, Smith RS, Araneda RC (2013). "α(1A)-Adrenergic regulation of inhibition in the olfactory bulb". J. Physiol. 591 (Pt 7): 1631–43. doi:10.1113/jphysiol.2012.248591. PMC 3624843. PMID 23266935.

"α_1A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2020-11-22. Retrieved 2008-11-25.
Human ADRA1A genome location and ADRA1A gene details page in the UCSC Genome Browser.

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