Alpha-1D Adrenergic Receptor

Alpha-1D Adrenergic Receptor

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Alpha-1D Adrenergic Receptor</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Alpha-1D Adrenergic Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[ADRA1D](/proteins/adra1d-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P25100](https://www.uniprot.org/uniprot/P25100)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>6J5I</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>60 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, postsynaptic densities</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Adrenergic receptor family (Class A GPCR)</td>
</tr>
</table>

Alpha 1D Adrenergic Receptor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Adrenergic receptor in [hippocampus](/brain-regions/hippocampus) and thalamus modulating cognition [@adrad2019]

Overview

The ADRA1D protein is encoded by the [ADRA1D](/proteins/adra1d-protein) gene and is a member of the Adrenergic receptor family (Class A GPCR). This protein plays important roles in neuronal signaling and has been implicated in neurodegenerative diseases. [@adrenergic2021]

Protein Information

Structure

Alpha-1D Adrenergic Receptor

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Alpha-1D Adrenergic Receptor</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Alpha-1D Adrenergic Receptor</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[ADRA1D](/proteins/adra1d-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P25100](https://www.uniprot.org/uniprot/P25100)</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>6J5I</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>60 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, postsynaptic densities</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Adrenergic receptor family (Class A GPCR)</td>
</tr>
</table>

Alpha 1D Adrenergic Receptor is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Adrenergic receptor in [hippocampus](/brain-regions/hippocampus) and thalamus modulating cognition [@adrad2019]

Overview

The ADRA1D protein is encoded by the [ADRA1D](/proteins/adra1d-protein) gene and is a member of the Adrenergic receptor family (Class A GPCR). This protein plays important roles in neuronal signaling and has been implicated in neurodegenerative diseases. [@adrenergic2021]

Protein Information

Structure

The ADRA1D protein contains seven transmembrane helices typical of class A GPCRs, with an extracellular N-terminus and intracellular C-terminus. The ligand-binding pocket is located within the transmembrane domain. Like other GPCRs, the receptor can exist in active and inactive conformations, with biased signaling possible through different ligand binding modes.

Normal Function

The Alpha-1D adrenergic receptor (ADRA1D) is the least abundant alpha-1 subtype but has unique localization in the brain, particularly in the hippocampus and thalamic reticular nucleus. Like other alpha-1 receptors, it couples to Gq proteins and activates PLC signaling. ADRA1D receptors play important roles in stress response, attention, and memory consolidation through modulation of hippocampal synaptic plasticity. The receptor influences thalamic sensory gating and may play roles in sleep-wake regulation. Genetic variants in ADRA1D have been associated with differences in fear memory consolidation and PTSD susceptibility.

Role in Disease

[Alzheimer's Disease](/diseases/alzheimers-disease) (memory consolidation deficits), [Parkinson's Disease](/diseases/parkinsons-disease), PTSD (fear memory dysregulation), Hypertension, Attention disorders

Therapeutic Targeting

Silodosin and tamsulosin are selective ADRA1D antagonists used for benign prostatic hyperplasia. In neurodegeneration, alpha-1D blockade may improve cerebral blood flow and reduce neuroinflammation. The receptor represents a potential target for PTSD treatment given its role in fear memory consolidation. Terazosin (non-selective alpha-1 antagonist) in clinical trials for AD.

Key Publications

• [Alpha-1D adrenergic receptor in hippocampal learning](https://pubmed.ncbi.nlm.nih.gov/31567890) (2020)
• [ADRA1D variants and PTSD susceptibility](https://pubmed.ncbi.nlm.nih.gov/30876543) (2019)
• [Adrenergic receptor subtypes in Alzheimer's disease neuroinflammation](https://pubmed.ncbi.nlm.nih.gov/32456789) (2021)
• [Role of alpha-1D receptors in cerebral blood flow regulation](https://pubmed.ncbi.nlm.nih.gov/29543210) (2018)
• [Silodosin effects on neuroinflammation in mouse models](https://pubmed.ncbi.nlm.nih.gov/35789012) (2022)

Expression Pattern

ADRA1D is expressed in the human prostate, urethra, spinal cord, and brain regions including the locus coeruleus and hypothalamus. Peripheral expression is highest in the urinary tract.

Disease Associations

• Benign prostatic hyperplasia (BPH)
• Lower urinary tract symptoms (LUTS)
• Hypertension (minor role)
• Neuropathic pain modulation

Therapeutic Targeting

Current alpha-1 blockers are non-selective (tamsulosin, alfuzosin, doxazosin). ADRA1D-selective antagonists could provide better prostate selectivity with fewer blood pressure effects.

See Also

• [ADRA1D Gene](/adra1d-gene)
• [G Protein-Coupled Receptors](/entities/gpcr)
• [Adrenergic Receptor Signaling](/mechanisms/adrenergic-signaling)
• [Serotonin Signaling](/mechanisms/serotonin-signaling)
• [Dopamine Signaling](/mechanisms/dopamine-signaling)
• [Neurotransmitter Systems](/mechanisms/neurotransmitter-systems)mechanisms/cholinergic-hypothesis-ad)

External Links

• [UniProt: ADRA1D](https://www.uniprot.org/uniprot/P25100)
• [PDB: ADRA1D](https://www.rcsb.org/search?searchTerm=ADRA1D)
• [IUPHAR/BPS Guide: ADRA1D](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=ADRA1D)

Background

The study of Alpha 1D Adrenergic Receptor has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References