TACR1 — Tachykinin Receptor 1

TACR1 — Tachykinin Receptor 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TACR1 — Tachykinin Receptor 1</th>
</tr>
<tr>
<td class="label">Tissue/Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Spinal cord</td>
<td>High</td>
</tr>
<tr>
<td class="label">Peripheral nerves</td>
<td>High</td>
</tr>
<tr>
<td class="label">Immune cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Gastrointestinal tract</td>
<td>High</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Gene Symbol: TACR1 Gene Name: Tachykinin Receptor 1 Chromosomal Location: 2p12 Aliases: NK1R, NK-1R, Substance P Receptor, SPR

Overview

TACR1 encodes the neurokinin 1 (NK1) receptor, a G protein-coupled receptor that binds substance P and other tachykinins. It is widely expressed in the central and peripheral nervous systems and plays important roles in pain transmission, neuroinflammation, mood regulation, and stress responses[@holmes2023].

Protein Structure and Function

The TACR1 receptor is a seven-transmembrane GPCR with the following characteristics:

TACR1 — Tachykinin Receptor 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TACR1 — Tachykinin Receptor 1</th>
</tr>
<tr>
<td class="label">Tissue/Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Spinal cord</td>
<td>High</td>
</tr>
<tr>
<td class="label">Peripheral nerves</td>
<td>High</td>
</tr>
<tr>
<td class="label">Immune cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Gastrointestinal tract</td>
<td>High</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Gene Symbol: TACR1 Gene Name: Tachykinin Receptor 1 Chromosomal Location: 2p12 Aliases: NK1R, NK-1R, Substance P Receptor, SPR

Overview

TACR1 encodes the neurokinin 1 (NK1) receptor, a G protein-coupled receptor that binds substance P and other tachykinins. It is widely expressed in the central and peripheral nervous systems and plays important roles in pain transmission, neuroinflammation, mood regulation, and stress responses[@holmes2023].

Protein Structure and Function

The TACR1 receptor is a seven-transmembrane GPCR with the following characteristics:

• Extracellular N-terminus: Contains ligand-binding sites
• Transmembrane domains: Seven alpha-helices spanning the membrane
• Intracellular C-terminus: Couples to G proteins and contains phosphorylation sites
• Ligand binding: High affinity for substance P (SP), with lower affinity for neurokinin A and B

Signal Transduction

Upon activation, TACR1 couples to:

• Gαq/11: Activates phospholipase C (PLC)
• IP3 production: Leads to intracellular Ca2+ release
• DAG formation: Activates protein kinase C (PKC)
• MAPK activation: Triggers downstream signaling cascades

Role in Neurodegeneration

Alzheimer's Disease

TACR1 and substance P have been implicated in Alzheimer's disease:

• Neuroinflammation: TACR1 activation promotes microglial activation and pro-inflammatory cytokine release
• Amyloid metabolism: Substance P may affect [amyloid precursor protein](/entities/app-protein) processing
• Cognitive function: NK1 receptor antagonists may have cognitive-enhancing effects
• Neuroprotection: Some studies suggest protective effects of substance P[@kramer2022]

Parkinson's Disease

In Parkinson's disease, TACR1 plays a role in:

• Motor function: Basal ganglia tachykinin signaling affects movement
• Neuroinflammation: Enhanced TACR1-mediated inflammation in the substantia nigra
• L-DOPA response: Potential involvement in treatment response and dyskinesias

Depression and Anxiety

TACR1 is a major target for substance P antagonists:

• Major depressive disorder: NK1 receptor antagonists show antidepressant effects
• Anxiety disorders: Anxiolytic potential of TACR1 modulation
• Stress response: TACR1 in stress-induced neurodegeneration

Pain and Migraine

• Pain transmission: TACR1 in nociceptive pathways
• Migraine: NK1 antagonists investigated for acute treatment

Expression Patterns

Therapeutic Implications

Drug Targets

TACR1 is a validated drug target:

• NK1 antagonists: Developed for depression, anxiety, and pain
• Substance P analogs: Therapeutic peptides
• Antiemetics: Aprepitant, fosaprepitant (approved for chemotherapy-induced nausea)

Clinical Applications

Interactions and Pathways

Protein Interactions

TACR1 interacts with:

• Substance P (TAC1): Primary endogenous ligand
• β-arrestin: Mediates receptor internalization
• RACK1: Scaffold protein
• PDZ domain proteins: Regulatory interactions

Signaling Pathways

• Phospholipase C pathway
• MAPK/ERK pathway
• [NF-κB](/entities/nf-kb) pathway
• Calcium signaling

Genetic Associations

Polymorphisms

TACR1 polymorphisms have been associated with:

• Depression susceptibility
• Pain perception
• Migraine risk
• Schizophrenia

Research

• Gene-environment interactions in mood disorders
• Pharmacogenetics of NK1 antagonists

Research Directions

Key Questions

Ongoing Studies

• TACR1 antagonists for neurodegenerative diseases
• Understanding neuroinflammation modulation
• Biomarker development

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References