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α1A-adrenoceptor

Previous and Unofficial Names
α1a
α1c
adrenergic receptor
Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 466 8p21-p11.2 ADRA1A
Rat 7 466 15p12 Adra1a
Mouse 7 466 14 D1 Adra1a
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Antagonists
Allosteric Regulators
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Database Links
ChEMBL Target 125 (Hs), 12271 (Mm), 12514 (Rn)
Ensembl ENSG00000120907 (Hs), ENSMUSG00000045875 (Mm), ENSRNOG00000009522 (Rn)
Entrez Gene 148 (Hs), 11549 (Mm), 29412 (Rn)
GeneCards ADRA1A (Hs)
HomoloGene 68078 (Hs)
OMIM 104221 (Hs)
PharmGKB Gene PA34 (Hs)
Protein Ontology (PRO) PRO:000001183 (Hs)
RefSeq Nucleotide NM_000680 (Hs), NM_013461 (Mm), NM_017191 (Rn)
RefSeq Protein NP_000671 (Hs), NP_038489 (Mm), NP_058887 (Rn)
UniGene Hs. 52931 (Hs)
UniProt P35348 (Hs), P97718 (Mm), P43140 (Rn)
Wikipedia α1A-adrenoceptor
Search for 3D structures on the PDB
Search using keywords: Adrenoceptors alpha1A-adrenoceptor Search using accession numbers: P43140 || P35348 || P97718
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]-HEAT Hs Full agonist 10.0 pKd 17
oxymetazoline Hs Full agonist 8.0 – 8.2 pKi 17,19-20
(-)-adrenaline Hs Full agonist 6.3 pKi 17
NS-49 Hs Partial agonist 6.2 pKi 19
noradrenaline Hs Full agonist 5.8 – 6.0 pKi 17,20
phenylephrine Hs Full agonist 5.2 – 5.4 pKi 20
methoxamine Hs Full agonist 5.0 – 5.2 pKi 17,20
(±)-adrenaline Hs Full agonist 5.0 pKi 17
A61603 Hs Full agonist 7.8 – 8.4 pIC50 4,18
Agonist Comments
The first α1A-adrenoceptor to be cloned was the bovine homolog. No species significant differences in pharmacology have been identified.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]BE-2254 Hs Antagonist 9.9 pKd 5,29
(-)-YM617 Hs Antagonist 10.7 pKi 17
KMD-3213 Hs Antagonist 10.4 pKi 17
tamsulosin Hs Antagonist 10.0 – 10.4 pKi 4,23,27-28
WB 4101 Rn Antagonist 10.2 pKi 22
NAN 190 Hs Antagonist 10.1 pKi 25
WB 4101 Hs Antagonist 9.7 – 9.8 pKi 4,17,23,28
Rec 15/2739 Hs Antagonist 9.6 pKi 4
RS-100329 Hs Antagonist 9.6 pKi 27
(+)-niguldipine Hs Antagonist 9.1 – 9.9 pKi 4,17
prazosin Rn Inverse agonist 9.5 pKi 22
prazosin Hs Inverse agonist 9.0 – 9.9 pKi 4,17,23,27-28
(+)-niguldipine Rn Antagonist 9.3 pKi 22
RS-17053 Hs Antagonist 9.2 – 9.3 pKi 4,23,28
5-methylurapidil Hs Antagonist 8.9 – 9.2 pKi 4,17,23-25
5-methylurapidil Rn Antagonist 9.0 pKi 22
Ro-70-0004 Hs Antagonist 8.9 pKi 27
SNAP5089 Hs Antagonist 8.8 pKi 3
A-119637 Hs Antagonist 8.6 pKi 26
A-119637 Rn Antagonist 8.6 pKi 26
phentolamine Hs Antagonist 8.6 pKi 17
roxindole Hs Antagonist 8.6 pKi 1
A-123189 Rn Antagonist 8.5 pKi 26
terguride Hs Antagonist 8.5 pKi 1
A-123189 Hs Antagonist 8.4 pKi 26
indoramin Hs Antagonist 8.4 pKi 4,28
risperidone Hs Antagonist 8.4 pKi 25
ritanserin Hs Antagonist 8.4 pKi 25
lisuride Hs Antagonist 8.3 pKi 1
spiperone Hs Antagonist 8.3 pKi 25
ketanserin Hs Antagonist 8.2 pKi 25
clozapine Hs Antagonist 8.1 pKi 25
phentolamine Rn Antagonist 8.1 pKi 22
(+)-cyclazosin Hs Antagonist 7.9 pKi 21
mianserin Hs Antagonist 7.6 pKi 25
cyproheptadine Hs Antagonist 7.4 pKi 25
spiroxatrine Hs Antagonist 7.3 pKi 25
BMY-7378 Rn Antagonist 7.0 pKi 26
BMY-7378 Hs Antagonist 6.9 – 7.0 pKi 25-26
cabergoline Hs Antagonist 6.5 pKi 1
piribedil Hs Antagonist 6.1 pKi 1
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) [3]. 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 [4].
Compounds designated as "partial inverse agonists" [5] are listed as neutral antagonists
Allosteric Regulator Comments
While no allosteric regulation of the α1A-adrenoceptor has been proven, possible allosteric enhancement has been shown with high concentrations of benzodiazepines. Amiloride analogs will increase the dissociation rate of prazosin from the α1A- adrenoceptor [2]

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
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.
References:  2,5
Secondary Transduction Mechanisms
Transducer Effector/Response
Phospholipase D stimulation
Other - See Comments
Comments:  α1-adrenoceptors (all subtypes) can also activate protein Kinase C, mitogen activated protein kinases.
References:  2,5
Tissue Distribution
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.
Species:  Human
Technique:  in situ hybridisation.
References:  9
High expression levels of α1A-adrenoceptor mRNA are found in the heart, liver, cerebelum and cerebral cortex
Species:  Human
Technique:  RNase Protection
References:  10
The α1A-adrenoceptor is the predominant subtype in human prostate and urethra.
Species:  Human
Technique:  Immunohistochemistry.
References:  11
Functional Assays
Isolated longitudinal strip of Vas Deferens.
Species:  Rat
Tissue:  Vas deferens
Response measured:  Contraction
References:  8
Isolated strips of prostate tissue containing both glandular and smooth muscle elements.
Species:  Human
Tissue:  Prostrate
Response measured:  Contraction
References:  4
Physiological Functions
Contraction of stromal and capsular smooth muscle to control urethral resistance.
Species:  Human
Tissue:  Prostate.
References:  13
Contraction of urethral smooth muscle.
Species:  Human
Tissue:  Urethra.
References:  14
Stimulation of myocyte hypertrophy.
Species:  Rat
Tissue:  Myocardium.
References:  15
Activation of sarcolemmal Na+-H+ exchanger.
Species:  Rat
Tissue:  Ventricular Myocytes.
References:  16
Contraction of skeletal muscle resistance arteries.
Species:  Human
Tissue:  Vasculature.
References:  12
Physiological Consequences of Altering Gene Expression
Cardiac specific overexpression of α1A-adrenoceptors enhanced cardiac contractility.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  6
Hypotension and a decreased pressor response to phenylephrine were observed in α1A- knockout mice.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  7

To cite this receptor data page, please use the following:

Richard A. Bond, David B. Bylund, Douglas C. Eikenburg, J. Paul Hieble, Rebecca Hills, Kenneth P. Minneman, Sergio Parra.
Adrenoceptors: α1A-adrenoceptor. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=22.


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