CCK-A (CCKAR) Neurons

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cell946 wordssynced 2026-04-02

CCK-A (CCKAR) Neurons

<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">CCK-A (CCKAR) Neurons</th>
</tr>
<tr>
<td class="label">Taxonomy</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology (CL)</td>
<td>[CL:0002277](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0002277)</td>
</tr>
<tr>
<td class="label">Database</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology</td>
<td>[CL:0002277](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0002277)</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Amygdala</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hypothalamus</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Variable</td>
</tr>
</table>

Introduction

Cck A (Cckar) Neurons is an important cell type in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

...

CCK-A (CCKAR) Neurons

Introduction

Overview

Neurons expressing the cholecystokinin A receptor (CCKAR) represent a significant population in both the peripheral and central nervous systems. CCKAR, also known as CCK-A receptor, is a G-protein coupled receptor that binds cholecystokinin (CCK) peptides with high affinity [@dufresne2006]. These neurons play crucial roles in anxiety regulation, memory formation, satiety signaling, and pancreatic function. CCKAR is distinct from the CCK-B receptor (CCKBR) in its distribution and function, with CCKAR primarily expressed in peripheral tissues and select brain regions.

Multi-Taxonomy Classification

Taxonomy Database Cross-References

External Database Links

[Cell Ontology (CL:0002277)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0002277)
[OBO Foundry (CL:0002277)](http://purl.obolibrary.org/obo/CL_0002277)
[Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
[CellxGene Census](https://cellxgene.cziscience.com/)
[Human Cell Atlas](https://www.humancellatlas.org/)

Taxonomy & Classification

External Database Links

[Cell Ontology (CL:0002277)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0002277)
[OBO Foundry (CL:0002277)](http://purl.obolibrary.org/obo/CL_0002277)
[Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
[CellxGene Census](https://cellxgene.cziscience.com/)

Molecular Biology of CCKAR

Gene and Protein Structure

The CCKAR gene is located on chromosome 4p15.2 in humans and encodes a 406-amino acid G-protein coupled receptor [@cckar]. The receptor protein contains:

N-terminal extracellular domain: Binds CCK peptides
Seven transmembrane domains: Characteristic of GPCRs
C-terminal intracellular domain: Couples to G proteins and initiates signaling

Ligands

CCKAR binds multiple forms of cholecystokinin:

CCK-8: Octapeptide, highest affinity for CCKAR
CCK-5: Pentapeptide variant
CCK-4: Tetrapeptide, primarily CCKBR ligand
Gastrin: Alternate ligand with lower affinity

Signaling Pathways

CCKAR activates multiple intracellular signaling cascades:

Phospholipase C (PLC) pathway: Increases IP3 and DAG, leading to calcium release

MAPK pathway: Regulates cell proliferation and differentiation

PI3K/Akt pathway: Involved in survival and growth

ERK1/2 activation: Mediates behavioral effects

Distribution in the Nervous System

Central Nervous System

CCKAR-expressing neurons are found in several brain regions:

Peripheral Nervous System

CCKAR is highly expressed in:

Pancreas: Pancreatic acinar cells
Gastrointestinal tract: Enteric neurons
Vagus nerve: Afferent signaling

Function in Normal Physiology

Anxiety and Emotion Regulation

CCKAR neurons in the amygdala and hippocampus play a key role in anxiety:

CCK acts as an anxiogenic peptide in the brain
CCKAR activation produces anxiety-like behaviors in animal models
CCKAR antagonists have anxiolytic properties [@bower2018]
The CCK system interacts with GABAergic signaling

Memory and Cognition

CCKAR in the cortex and hippocampus modulates memory processes:

CCK enhances memory consolidation
CCKAR activation improves spatial memory in some studies
Interaction with NMDA receptors affects synaptic plasticity
May play a role in age-related cognitive decline

Satiety and Feeding

In the hypothalamus, CCKAR neurons regulate appetite:

CCK is released from the gut during meals
CCKAR activation signals satiety to the brain
CCKAR antagonists can increase food intake
Important for meal termination

Pancreatic Function

In the pancreas, CCKAR regulates digestive enzyme secretion:

CCK stimulates pancreatic acinar cell secretion
Important for fat digestion
Dysregulation may contribute to pancreatic disorders

Role in Neurodegenerative Diseases

Alzheimer's Disease

CCKAR dysfunction is increasingly recognized in Alzheimer's disease:

CCK System Changes:

Altered CCK levels in AD patients
Reduced CCKAR expression in the hippocampus
May contribute to memory impairment

Relationship with Amyloid:

CCK neurons may be vulnerable to amyloid pathology
Amyloid may disrupt CCK signaling
Therapeutic targeting is being explored [@meyerlindenberg1997]

Therapeutic Potential:

CCKAR agonists may improve cognition
CCK/CCKAR-based strategies under investigation

Parkinson's Disease

The CCK system may be affected in Parkinson's disease:

Altered CCK levels in the substantia nigra
May modulate dopaminergic neuron function
Possible role in non-motor symptoms

Anxiety Disorders

Given CCKAR's role in anxiety:

CCKAR polymorphisms associated with panic disorder
CCKAR antagonists being developed as anxiolytics
Potential for personalized medicine approaches

Therapeutic Targeting

CCKAR Agonists

Potential Applications:

Cognitive enhancement
Appetite regulation
Pancreatic insufficiency treatment

CCKAR Antagonists

Clinical Use:

Devazepide: Research compound, anxiolytic potential
Lintitript: CCK antagonist investigated for anxiety

Development Status:

Clinical trials for anxiety disorders
Investigated for pancreatic disorders
May have cognitive benefits

Research Tools

Devazepide: Selective CCKAR antagonist
A-71623: CCKAR agonist
SR 27897: CCKAR antagonist

Cross-Linking and Related Topics

Related Genes and Proteins

CCK Gene - Cholecystokinin
CCKBR Gene - CCK B receptor
GABA Receptors
NMDA Receptor

Related Cell Types

Cortical Pyramidal Neurons
Hippocampal CA1 Neurons
Amygdala Neurons
Hypothalamic Neurons

Related Diseases

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

Related Mechanisms

[Synaptic Plasticity](/mechanisms/synaptic-dysfunction)
Anxiety Mechanisms
Appetite Regulation

Background

The study of Cck A (Cckar) Neurons 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.

External Links

NCBI Gene: [CCKAR](https://www.ncbi.nlm.nih.gov/gene/886)
UniProt: [CCKAR](https://www.uniprot.org/uniprot/P32297)
Ensembl: [CCKAR](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000163394)
IUPHAR: [CCKAR receptor](https://www.guidetopharmacology.org/1408)
PubMed: [CCKAR neurodegeneration research](https://pubmed.ncbi.nlm.nih.gov/?term=CCKAR+neurodegeneration)

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