Gastrin: Structure, Function, Control and Physiological Effects

It is an essential physiological regulator of gastric acid secretion.

It also has an important trophic or growth-promoting influence on the gastric mucosa. It is synthesized in G cells, located in gastric pits, and binds to receptors predominantly in parietal cells and enterochromaffin type.

Structure and definition of gastrin

Gastrin is a linear peptide synthesized as a preprohormone and cleaved post-translationally to form a family of peptides with identical carboxy thrill.

The predominant circulating form is gastrin-34 (“large gastrin”), but total biological activity is present in the smaller peptide (gastrin-14 or minigastrin).

In addition, full bioactivity is conserved in the five C-terminal amino acids of gastrin, which is known as pentagastrin. The five C-terminal amino acids of gastrin and cholecystokinin are identical, which explains their overlapping biological effects.

The gastrin receptor is also one of the receptors that bind to cholecystokinin and is known as the CCK-B receptor.

It is a member of the family of receptors coupled to G proteins. The gastrin binding stimulates an increase in intracellular Ca ++, the activation of protein kinase C and the production of inositol phosphate.


Control and physiological effects

The primary stimulus for gastrin secretion is the presence of certain foods, especially peptides, certain amino acids, and calcium.

In addition, compounds not yet identified in coffee, wine, and beer are potent stimulants of gastrin secretion. The secretion of this hormone is inhibited when the luminal pH of the stomach becomes very low.

Gastrin seems to have at least two main effects on gastrointestinal function:

Stimulation of gastric acid secretion: gastrin receptors are found in parietal cells, and gastrin binding, together with histamine and acetylcholine, leads to the secretion of acid fully stimulated by these cells.

Canine parietal cells have approximately 44,000 gastrin receptors each, and in that species, the immunoneutralization of gastrin has been shown to block acid secretion in response to intragastric peptide administration.

Enterochromaffin-like cells (ECL) also carry gastrin receptors. Recent evidence indicates that this cell may be the most crucial goal of gastrin concerning the regulation of acid secretion.

The stimulation of ECL cells by gastrin leads to histamine release, and the binding of histamine to H2 receptors in parietal cells is necessary for the complete realization of acid secretion.

Promotion of the growth of the gastric mucosa: gastrin can stimulate many aspects of mucosal development and growth in the stomach.

Treatment with gastrin stimulates the synthesis of DNA, RNA, and proteins in the gastric mucosa and increases the number of parietal cells.

Another observation that supports this function is that humans with hypergastrinemia (abnormally high blood levels of gastrin) consistently show hypertrophy of the gastric mucosa.

In addition to parietal cells and ECL targets, gastrin also stimulates pancreatic acinar cells by binding to cholecystokinin receptors. Gastrin receptors have been demonstrated in specific populations of gastric smooth muscle cells, supporting pharmacological studies showing that pharmacological studies indicate a role of gastrin in regulating gastric motility.

How is gastrin controlled?

Before a meal, the nerves within the brain responsible for the stomach are stimulated by stimulating the release of gastrin.

The stretching of the stomach walls also stimulates the release of gastrin during a meal, the presence of certain foods (mainly proteins) within the stomach cavity, and an increase in the pH levels of the stomach (i.e., the belly becomes less acidic).

The production and release of gastrin slow down with the hormone somatostatin, which is released when the stomach empties at the end of a meal and when the pH of the stomach becomes too acidic (pH less than 3).

What happens if I have too much gastrin?

An excess may occur due to a gastrin-secreting tumor (gastrinoma, also known as Zollinger-Ellison syndrome).

In gastrinomas, high levels of gastrin that move around the intestine stimulate the release of acid, which causes ulcers in the stomach and small intestine that can burst.

High levels of stomach acid can also cause diarrhea because the small intestine lining is damaged.

High levels of circulating gastrin can also occur when the pH of the stomach is high (i.e., it is not acidic enough), for example, in pernicious anemia or atrophic gastritis when the lining of the stomach is damaged and can not produce and release acid, and during treatment with antacid medications.

As gastrin also stimulates the growth of the stomach lining, it is believed that high levels of this may play a role in the development of certain cancers of the digestive tract. However, this has not been proven.

What happens if I have very little gastrin?

It is rare to have very little gastrin. However, low levels of gastric acid may increase the risk of infection within the intestine and may limit the ability of the stomach to absorb nutrients.