Cholecystokinin (CCK) is a peptide hormone synthesised by L-cells in the mucosal epithelium of the duodenum, and secreted in response to the presence of partially digested lipids and proteins. CCK inhibits gastric emptying and stimulates the release of digestive enzymes from the pancreas and bile from the gall bladder by acting at CCK-1 receptors (formerly known as CCK-A receptors, these are mainly found in the periphery, including on vagal afferent nerve endings but are also found in some areas of the CNS). Because gastric emptying is inhibited, the partially digested lipids and proteins are exposed to the digestive enzymes and bile so are further broken down. As the lipids and proteins are broken down, CCK secretion declines.
CCK acts as a ‘gatekeeper’ for the response of other gut-brain signalling hormones on the afferent vagal neurons. At low levels (after fasting), CCK stimulates the expression of receptors associated with the stimulation of food intake, including receptors for melanin concentrating hormone (MCH)-1 and [[cannabinoid] CB1 receptors. At high levels (after food consumption), MCH-1 and CB1 receptors are down-regulated. Therefore CCK present at a high or low concentration can affect how afferent vagal neurons respond to other neurohormones.
In rats, CCK inhibits food intake in younger individuals more effectively than in older individuals. It also has a greater effect in males than in females.
Diseases resulting from excessive or deficient secretion of cholecystokinin are rare in humans. Cholecystokinin deficiency has been described as part of autoimmune polyglandular syndrome, and was manifest as a malabsorption syndrome similar to pancreatic exocrine insufficiency. There is some evidence that aberrations in expression of cholesystokinin or its receptor within the brain might be involved in certain types of anxiety and schizophrenia.