Cholecystokinin

Cholecystokinin (CCK) is a neurotransmitter important in the regulation of satiety and a gastrointestinal hormone responsible for the digestion fats and proteins. There are several molecular forms of CCK, although they are all products of the same gene. As a hormone, CCK is produced in the endocrine cells lining the upper parts of the small intestine. Gastrointestinal CCK receptors are found in the pancreas, gallbladder, stomach, lower esophagus, the end of the small intestine, and the colon. As a neurotransmitter, CCK is most highly concentrated in dopamine-containing neurons in the cerebral cortex, although it can be found in the midbrain as well. CCK is also seen in peripheral nerves innervating the intestines and the vagus nerve. CCK neuroreceptors are found in the brain and gastrointestinal peripheral nerves.

After a meal, especially one that is high in protein or fat, the digested products of fat, protein, and carbohydrates cause CCK release. CCK blood levels peak within 15 minutes and gradually decrease over the next 3 to 5 hours. The half-life of CCK in the blood is 1 to 2 minutes.

When released, CCK's primary role is to stimulate contraction of the gallbladder, facilitating bile secretion into the small intestine to break down fats. CCK stimulates the pancreas to release enzymes into the small intestine that break down proteins. Additionally, CCK also inhibits stomach acid secretion.

CCK regulates bowel motility by delaying emptying of the stomach, increasing satiation and decreasing food intake. Although CCK decreases meal size and duration, it does not alter satiety between meals. As a result, drugs mimicking CCK are not seen as an effective strategy for long-term obesity management because they do not inhibit hunger in a sustainable way. In fact, while CCK infusions reduce food intake, they also reduce the interval between meals such that energy intake returns to baseline within days.

CCK1 is a CCK receptor important in appetite control. When high concentrations of CCK bind to CCK1, appetite is suppressed. However, increased fat intake, while resulting in high concentrations of CCK, also reduces CCK1 sensitivity to CCK. Thus, the satiating effect of CCK is similar in normal weight and obese patients. Selective CCK1 antagonists are used to increase hunger in treatments of anorexia and cachexia.