Cholecystokinin (Cck), a neuropeptide and gut hormone, has diverse essential functions. It modulates digestion, glucose levels, neurotransmitters, and memory [1,2]. Cck is involved in pathways related to gastric acid and digestive enzyme secretion, gut motility, satiety, and neurotransmission. It binds to two main receptors, CCK-1R and CCK-2R, and its physiological importance is underscored by its presence in the brain-gut axis, making it a significant area of study for understanding various biological processes. Genetic models, such as KO or CKO mouse models, could potentially provide deeper insights into its function.

CCK-1R stimulation by sulphated CCK-8 elicits dopamine release in the substantia nigra and striatum [1]. Activation of hippocampal and nigral CCK-2Rs is neuroprotective, evoking AMPK activation, expression of mitochondrial fusion modulators, and autophagy, suggesting potential therapeutic applications in Alzheimer's and Parkinson's disease [1]. Cck also acts as a peripheral satiety signal, acting either via the vagus or directly on the dorsal medulla via CCK-1R [2]. In the context of anxiety and cognitive processes, selective CCK-B agonists and antagonists have different effects on anxiety-like behaviors, and Cck may offer new perspectives in treating attention and memory disorders [3]. Cck is involved in pancreatic function and morphology, and CCK-A antagonists can cause slight hypotrophy and hypoplasia of the exocrine pancreas [4]. In colonic motor function, Cck, through CCK-1 receptors, may contribute to symptoms of functional gastrointestinal disorders, and CCK-1 receptor antagonists are being developed for treating constipation-predominant IBS [5]. In nociception, Cck may act as an endogenous opiate antagonist, and CCK antagonists enhance morphine analgesia in rats [6]. Cck is also involved in the control of feeding, with both CCK-A and CCK-B receptors playing roles in mediating satiety [7].

In conclusion, Cck plays crucial roles in multiple biological processes including digestion, neurotransmission, satiety, pain modulation, and feeding. Model-based research, especially potentially through KO/CKO mouse models, has the potential to further clarify its functions and offers significant promise for understanding and potentially treating diseases such as neurodegenerative diseases, functional gastrointestinal disorders, and pain-related conditions.