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 [1]. 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.
The CCKAR gene is located on chromosome 4p15.2 in humans and encodes a 406-amino acid G-protein coupled receptor [2]. The receptor protein contains:
CCKAR binds multiple forms of cholecystokinin:
CCKAR activates multiple intracellular signaling cascades:
CCKAR-expressing neurons are found in several brain regions:
| Brain Region | Expression Level | Function |
|---|---|---|
| Cortex | Moderate | Cognitive processing |
| Hippocampus | High | Memory, anxiety |
| Amygdala | High | Emotion regulation |
| Hypothalamus | Moderate | Satiety, homeostasis |
| Brainstem | Variable | Visceral functions |
CCKAR is highly expressed in:
CCKAR neurons in the amygdala and hippocampus play a key role in anxiety:
CCKAR in the cortex and hippocampus modulates memory processes:
In the hypothalamus, CCKAR neurons regulate appetite:
In the pancreas, CCKAR regulates digestive enzyme secretion:
CCKAR dysfunction is increasingly recognized in Alzheimer's disease:
CCK System Changes:
Relationship with Amyloid:
Therapeutic Potential:
The CCK system may be affected in Parkinson's disease:
Given CCKAR's role in anxiety:
Potential Applications:
Clinical Use:
Development Status:
Dufresne, M., et al. (2006). Cholecystokinin and gastrin receptors. Physiological Reviews, 86(3), 805-847 ↩︎
Bower, R.L., et al. (2018). CCK receptor signaling: From neuropsychiatry to cancer. Trends in Pharmacological Sciences, 39(8), 721-735 ↩︎
Meyer-Lindenberg, A., et al. (1997). Cholecystokinin in the cerebrospinal fluid: decreased concentrations in patients with Alzheimer's disease. Journal of Neural Transmission, 104(4-5), 457-464 ↩︎