cholecystokinin signaling pathway

Definition

Target type: biologicalprocess

A G protein-coupled receptor signaling pathway initiated by cholecystokinin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:jc, PMID:11181948]

The cholecystokinin (CCK) signaling pathway is a complex and multifaceted process that plays a crucial role in regulating various physiological functions, primarily in the gastrointestinal system. It begins with the release of CCK, a peptide hormone, from endocrine cells in the small intestine in response to the presence of dietary fats and proteins. Once released, CCK binds to its specific receptor, the CCK receptor (CCKR), which is a G protein-coupled receptor (GPCR) found on the surface of various cells, including pancreatic acinar cells, gallbladder smooth muscle cells, and neurons in the brain.

The binding of CCK to CCKR triggers a cascade of intracellular signaling events:

1. **Activation of G proteins:** CCKR activation leads to the activation of heterotrimeric G proteins, specifically the Gq/11 subtype. This activation results in the dissociation of the α subunit of the G protein, which then activates phospholipase C (PLC).

2. **Production of inositol triphosphate (IP3) and diacylglycerol (DAG):** PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into IP3 and DAG, which act as second messengers.

3. **Calcium signaling:** IP3 binds to IP3 receptors on the endoplasmic reticulum (ER), leading to the release of intracellular calcium (Ca2+). The increased Ca2+ concentration activates various downstream signaling pathways, including protein kinase C (PKC) activation and Ca2+-dependent exocytosis.

4. **Activation of protein kinase C (PKC):** DAG activates PKC, a serine/threonine kinase, which phosphorylates various target proteins, thereby modulating their activity and ultimately contributing to the overall cellular response.

5. **Cellular responses:** The activation of the CCK signaling pathway leads to a variety of cellular responses depending on the cell type and context:

* **Pancreatic acinar cells:** CCK signaling stimulates the release of digestive enzymes, such as amylase, lipase, and protease, from pancreatic acinar cells. This process facilitates the digestion of dietary fats and proteins.
* **Gallbladder smooth muscle cells:** CCK signaling induces the contraction of gallbladder smooth muscle cells, leading to the release of bile into the duodenum. Bile is essential for the digestion and absorption of fats.
* **Brain neurons:** CCK signaling in the brain plays a role in regulating food intake, satiety, and anxiety. It also contributes to the regulation of gastrointestinal motility and pancreatic secretion.

The CCK signaling pathway is a critical regulator of digestion, nutrient absorption, and other physiological processes. Dysregulation of this pathway can contribute to various gastrointestinal disorders, including pancreatitis, cholelithiasis, and irritable bowel syndrome. Therefore, understanding the complexities of CCK signaling is crucial for developing therapeutic strategies for these conditions.'
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Proteins (4)

Compounds (34)