Cholecystokinin (CCK) is a hormone secreted in the intestine and activated in response to the ingestion of certain foods. It intervenes in processes such as digestion and appetite, generating a feeling of satiety that helps us regulate our appetite.

In this article we explain in more detail what this hormone is and what functions it performs, how the satiety effect is produced and what the latest research says about its possible role in preventing cognitive impairment.

What is cholecystokinin?

Cholecystokinin is produced in the small intestine, specifically in the duodenum and jejunum, and causes contraction of the gallbladder and pancreatic secretion. This hormone is also considered a neurotransmitter that is released in the nervous system , especially in the hypothalamus.

This hormone belongs to the group of quinines, which are formed from globulins (a group of water-soluble proteins present in animals and plants) by proteolytic enzymatic action. Proteolysis consists of the degradation of proteins, either by specific enzymes or through intracellular degradation.

The secretion or production of cholecystokinin depends on factors such as the presence of some nutrients from the foods lodged in the intestine , mainly fats and proteins (fatty acids and amino acids).

Functions

Cholecystokinin has several functions, both in its role as a gastrointestinal hormone and as a neurotransmitter in the nervous system.

As a gastrointestinal hormone

Cholecystokinin, together with gastrin and secretin, constitutes one of the main hormones secreted at the gastrointestinal level. It is known that the secretion of CCK and its effects on gastric motility depend on ingested fats , specifically on the length of the fatty acid chain.

  • CCK acts as a signal of satiety and once released has multiple effects on the gastrointestinal system, performing the following functions:
  • It causes the contraction of the gallbladder, facilitating the excretion of bile into the duodenum, which intervenes in the digestion processes.
  • It stimulates the secretion of hydrochloric acid in the stomach to aid digestion by breaking down food.
  • It regulates the pancreatic secretion of enzymes and hormones, such as insulin and glucagon, regulating the production of glucose in the liver and blood.
  • It stimulates relaxation and the opening of the sphincter of Oddi, a muscle that opens in response to food so that bile and pancreatic digestive juices enter the duodenum and mix with food to make digestion.

As a neurotransmitter

Cholecystokinin has also been found in the brain (mainly in the cortex, but also in other areas such as the retina, the hippocampus, the hypothalamus and the spinal cord) and plays a role as a neurotransmitter or neuromodulator, acting on the neurons of the periaqueductual grey matter, which are related to pain perception, and on the neurons of the medial hypothalamus, which are responsible for controlling food intake.

CCK levels usually rise towards the end of the meal , triggering the mechanisms of satiety. The presence of CCK in the amygdala and in some areas of the cerebral cortex, has led researchers to suggest that this hormone may have a role related to emotions.

Cholecystokinin has also been found to have an anxiety-causing function in the brain, as several studies have shown that injecting agonists into one of the CCK receptors produces autonomic and behavioral changes associated with sensations such as fear and anxiety, while antagonistic substances cause the opposite.

CCK, moreover, seems to interact at the synapses with another neurotransmitter, dopamine , especially in the nigrostriatal fibres that innervate the striatum and the nucleus accumbens, a brain structure involved in reward systems and responsible for integrating motivational information with emotions and motor actions.

CCK and the satiety effect

Cholecystokinin (CCK) is the best studied satiety inducing peptide . Let’s see below how this effect is produced.

CCK is secreted by the I cells of the mucosa of the duodenum and jejunum in response to the presence of partially digested fats and carbohydrates from the stomach.

This hormone, as previously mentioned, causes the contraction of the gallbladder, the release of pancreatic enzymes, the inhibition of motility and gastric emptying , thus decreasing the size of the food ingested.

Cholecystokinin secretion is activated by the presence of degradation products of fats, peptides, amino acids and, to a lesser extent, dietary carbohydrates; and inhibited by the intestinal concentration of pancreatic proteases (trypsin and chymotrypsin) and bile, after the ingestion of a food.

The CCK produces the contraction of the pylorus (the lower opening of the stomach that communicates with the small intestine), generating a gastric distension that activates the vaginal afferences that relieve the nucleus of the solitary tract to finally stimulate the center of satiety; a satiety effect that lasts, approximately, 90 minutes.

Recent research

Recent research by scientists at the University of Iowa in the United States suggests that a high level of cholecystokinin may decrease a person’s chance of developing Alzheimer’s disease .

The researchers conducted a study with 287 subjects and chose this hormone, which in the brain acts as a neurotransmitter, for its high expression in the formation of a cognitive process such as memory.

Its aim was to detect whether there is a relationship between cholecystokinin levels and memory, and the state of the grey matter in the hippocampus and other related brain areas.

At the same time, neuroscientists studied tau proteins (whose accumulation is linked to the development of Alzheimer’s disease), with the aim of observing how they might interact with cholecystokinin and memory.

The results of the study concluded that, as tau protein levels increased, an equally high level of cholecystokinin was no longer associated with less memory impairment .

This research highlights the importance of studying the nutritional aspect of diets, as well as their relationship with mental health and their involvement in the prevention of cognitive impairment and neurodegenerative disorders such as Alzheimer’s disease.

Bibliographic references:

  • González Hita ME, Ambrosio Macías KG, Sánchez Enríquez S. Neuroendocrine regulation of hunger, satiety and maintenance of energy balance. Inv Sal 2006;3:191-200.
  • Murahainen N, Kissileff HR, Derogatis AJ, Pi-Sunyer FX. “Efectos del colecistoquinina-octapéptido (CCK-8) en la ingesta de alimentos y el vaciado gástrico en el hombre”. Physiol Beba, 1988; 44:645-649.
  • Plagman, A., Hoscheidt, S., McLimans, K. E., Klinedinst, B., Pappas, C., Anantharam, V., … & Iniciativa de Neuroimágenes de la Enfermedad de Alzheimer. (2019). La colecistoquinina y la enfermedad de Alzheimer: un biomarcador de la función metabólica, la integridad neural y el rendimiento cognitivo. Neurobiología del envejecimiento, 76, 201-207.