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α1D-adrenoceptor

Previous and Unofficial Names
α1a/d-adrenoceptor
α1A-adrenoceptor
adrenergic receptor
Structural Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 572 20p13 ADRA1D 47
Rat 7 561 3q36 Adra1d 32
Mouse 7 562 2 F1 Adra1d 30
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
Receptor Comments
Database Links
ChEMBL Target 103 (Hs), 10646 (Mm), 12742 (Rn)
Ensembl ENSG00000171873 (Hs), ENSMUSG00000027335 (Mm), ENSRNOG00000021256 (Rn)
Entrez Gene 146 (Hs), 11550 (Mm), 29413 (Rn)
GeneCards ADRA1D (Hs)
OMIM 104219 (Hs)
PharmGKB Gene PA24597 (Hs)
Protein Ontology (PRO) PRO:000001185 (Hs)
RefSeq Nucleotide NM_000678 (Hs), NM_013460 (Mm), NM_024483 (Rn)
RefSeq Protein NP_000669 (Hs), NP_038488 (Mm), NP_077809 (Rn)
UniGene Hs. 557 (Hs)
UniProt P25100 (Hs), P97714 (Mm), P23944 (Rn)
Wikipedia α1D-adrenoceptor
Search for 3D structures on the PDB
Search using keywords: Adrenoceptors alpha1D-adrenoceptor Search using accession numbers: P23944 || P25100 || P97714
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 9.5 pKd 17
(-)-noradrenaline Hs Full agonist 7.4 pKi 17
(-)-adrenaline Hs Full agonist 7.2 pKi 17
cirazoline Rn Full agonist 6.9 pKi 34
clonidine Rn Full agonist 6.9 pKi 34
St 587 Rn Full agonist 6.5 pKi 34
oxymetazoline Hs Partial agonist 6.4 pKi 17,19
noradrenaline Rn Full agonist 6.3 pKi 34
(±)-adrenaline Rn Full agonist 6.3 pKi 34
oxymetazoline Rn Partial agonist 6.2 pKi 34
SKF 89748 Rn Full agonist 6.1 pKi 34
6-fluoro-noradrenaline Rn Full agonist 6.0 pKi 34
(±)-adrenaline Hs Full agonist 6.0 pKi 17
xylometazoline Rn Full agonist 6.0 pKi 34
phenylephrine Rn Full agonist 5.9 pKi 34
α-methylnoradrenaline Hs Full agonist 5.6 pKi 34
Sgd 101/75 Rn Full agonist 5.5 pKi 34
NS-49 Hs Partial agonist 5.4 pKi 19
methoxamine Hs Full agonist 4.9 pKi 17
methoxamine Rn Full agonist 4.5 pKi 34
amidephrine Rn Full agonist 4.2 pKi 34
View species-specific agonist tables
Agonist Comments
Non catecholamine agonists, such as methoxamine and amidephrine, have both low affinity and low intrinsic activity at the α1D- adrenoceptor[34].
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 29
(-)-YM617 Hs Antagonist 10.2 pKi 17
tamsulosin Hs Antagonist 9.8 – 10.1 pKi 4,27
prazosin Hs Inverse agonist 9.5 – 10.2 pKi 4,17,27
A-123189 Rn Antagonist 9.8 pKi 26
A-119637 Rn Antagonist 9.7 pKi 26
A-119637 Hs Antagonist 9.6 pKi 26
WB 4101 Hs Antagonist 9.6 pKi 4,17
A-123189 Hs Antagonist 9.5 pKi 26
NAN 190 Hs Antagonist 9.2 pKi 25
BMY-7378 Rn Antagonist 9.0 pKi 26
BMY-7378 Hs Antagonist 8.7 – 9.1 pKi 25-26
KMD-3213 Hs Antagonist 8.7 pKi 17
(+)-cyclazosin Hs Inverse agonist 8.5 pKi 21
phentolamine Hs Inverse agonist 8.2 pKi 17
spiperone Hs Antagonist 8.1 pKi 25
RS-100329 Hs Antagonist 7.9 pKi 27
spiroxatrine Hs Antagonist 7.9 pKi 25
ketanserin Hs Antagonist 7.8 pKi 25
Rec 15/2739 Hs Antagonist 7.8 pKi 4
ritanserin Hs Antagonist 7.8 pKi 25
RS-17053 Hs Antagonist 7.8 pKi 4
clozapine Hs Antagonist 7.7 pKi 25
(+)-cyclazosin Rn Inverse agonist 7.6 pKi 21
5-methylurapidil Hs Antagonist 7.1 – 8.0 pKi 4,17,25
mianserin Hs Antagonist 7.5 pKi 25
(+)-niguldipine Hs Antagonist 7.4 pKi 4,17
risperidone Hs Antagonist 7.4 pKi 25
Ro-70-0004 Hs Antagonist 7.2 pKi 27
SKF 105854 Hs Antagonist 7.1 pKi 65
cyproheptadine Hs Antagonist 6.9 pKi 25
indoramin Hs Antagonist 6.7 pKi 4
View species-specific antagonist tables
Antagonist Comments
Although cyslazosin does not show selectivity in radioligand binding assays with recombinant α1-adrenoceptors, functional selectivity for the α1D-adrenoceptor is observed in functional assays using isolated tissue assays measuring affinity for native α1- subtypes [49].
Differentiation between neutral antagonists and inverse agonists at the α1D- adrenoceptor has not been studied extensively.
Allosteric Regulator Comments
Lorazepam and midazolam have been shown to increase the maximum response to phenylephrine in cells expressing the human α1D-adrenoceptor[48].

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 α1D-adrenoceptor is coupled to calcium release and inositol phosphate production less efficiently than either the α1A- or α1B-adrenoceptor.
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
α1D- adrenoceptor message and protein is predominant in human bladder.
Species:  Human
Technique:  RNase protection assay, RT-PCR.
References:  50
In the rat brain, highest levels of α1D-adrenoceptor message are found in the olfactory bulb, cerebral cortex, hippocampus, dentate gyrus, reticular thalamic nucleus, motor neurons and the inferior olivary complex. In the thalamus, the α1B and α1D-adrenoceptors have a complimentary distribution.
Species:  Rat
Technique:  in situ hybridisation.
References:  58
The α1D-adrenoceptor was the predominant α1 subtype in the human aorta, but either had the lowest expression of the three subtypes, or was not detectable, in other arteries and veins. However, another report showed high expression of α1D-adrenoceptor in blood vessels of human prostate.
Species:  Human
Technique:  RNAse Protection, immunohistochemistry.
References:  11,59
Functional Assays
Isolated rat aortic ring.
Species:  Rat
Tissue:  Vasculature.
Response measured:  Contraction.
References:  56
Skeletal muscle arteriole.
Species:  Rat
Tissue:  Vasculature.
Response measured:  Contraction.
References:  57
Physiological Functions
Contraction of mesenteric resistance arteries.
Species:  Rat
Tissue:  Vasculature.
References:  5
α1D-adrenoceptors mediate nerve stimulated contraction of corpus cavernosa.
Species:  Rat
Tissue:  Corpus Cavernosa.
References:  60
Coronary artery vasoconstriction.
Species:  Mouse
Tissue:  Vasculature.
References:  41
Femoral artery vasoconstriction.
Species:  Rat
Tissue:  Vasculature.
References:  61
Locomotor activity in response to environmental stimulation.
Species:  Mouse
Tissue:  Brain.
References:  62
Reflex evoked urethral contraction.
Species:  Rat
Tissue:  Urethra.
References:  63
Endothelium dependent vasodilation of mesenteric vascular bed.
Species:  Rat
Tissue:  Vasculature.
References:  64
Physiological Consequences of Altering Gene Expression
α1D knockout mice had delayed tail-flick and hindpaw-licking responses to thermal stimuli.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  53
α1D knockout mice had hypotension, a decreased pressor and decreased coronary vasoconstrictor response to phenylephrine and resistance to salt induced hypertension.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  41,54-55
Receptor Comments
α1D- adrenoceptor message and protein is predominant in human bladder [50]. In bladder tissue from normal rats, only 25% of α1- adrenoceptor message was of the α1D- subtype; however following bladder obstruction, this percentage increased to 75% [51].
When recombinant α1D- adrenoceptors are expressed in fibroblast cell lines, most of the expression is intracellular, as opposed to the cell surface expression of the other α1 subtypes [52].

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: α1D-adrenoceptor. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=24.


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