GASTRINA: CHARACTERISTICS, STRUCTURE, PRODUCTION, FUNCTIONS - BIOLOGY - 2025

The gastrin is a gastric hormone that is produced proteinaceous into the stomach cavity of many mammals and whose functions are related to stimulation of the secretion of gastric acid and enzymes.

It is produced by a group of endocrine cells known as “G” (gastrin) cells, which are found in the pyloric glands in the most distal part of the stomach (antrum) and in the proximal region of the duodenum (see image).

Simplified diagram of the human stomach (Source: Estomago.svg: Rhcastilhosderivative work: Estevoaei via Wikimedia Commons)

Histologically speaking, G cells have a characteristic "flask" shape, with a broad base and a "neck" that reaches the surface of the stomach lining.

Since 1905 the existence of gastrin has been suspected. However, it was not until 1964 that this "antral hormone" (because it is produced in the antrum of the stomach) was isolated for the first time thanks to the work of Gregory and Tracy, who studied the stomach mucosa of pigs.

Its chemical structure was elucidated shortly after by Kenner and collaborators, who were also responsible for artificially synthesizing it.

Like other hormones of the mammalian endocrine system, gastrin is the product of co-translational enzymatic processing of a precursor molecule known as preprogastrin.

Their functions depend on their interaction with specific receptors that usually trigger intracellular signaling cascades related to G-proteins and protein kinases (phosphorylation cascades).

The concentration of intracellular calcium, the presence of acids and amino acids in the stomach lumen, or nerve stimulation through specific neurotransmitters are some of the factors that control the secretion of this important hormone in humans.

characteristics

Gastrin is a peptide-like hormone and since its discovery until today, three forms of this molecule have been recognized and are named, according to their size:

- Gastrina "grande" (from English "Big gastrin") of 34 amino acids

- Gastrin "small" (from English "Little gastrin") of 17 amino acids

- Gastrina "miniature" or "mini gastrina" (from the English "Mini gastrin") of 13 amino acids.

Large gastrin is found in the antral mucosa and has also been identified in extracts from human gastrinomas (stomach tumors). Some authors consider that both small and miniature gastrin correspond to fragments derived from it.

Structure of the «large gastrin» G-34 (Source: Edgar181 via Wikimedia Commons)

Obtaining the amino acid sequence of large gastrin has served as evidence to verify the previous hypothesis, since the C-terminal peptide heptadeca of the sequence of this peptide is identical to the sequence of small gastrin.

Furthermore, the trideca-peptide sequence of the C-terminus of small gastrin is identical to the amino acid sequence of miniature gastrin or miniature gastrin, 13 amino acids long.

In small gastrin (G17), the fragment identical to mini gastrin (C-terminal trideca peptide end) has been determined to have biological activity, but the N-terminal end is biologically inactive.

It is now known that this protein undergoes a series of co-translational modifications that involve enzymatic cleavage of the "precursor" form (large gastrin or G-34) for the production of the active peptide heptadeca (small gastrin) and other derivatives. little ones.

Structure

The types of gastrin mentioned above (G-34, G-17 and G-13) are linear peptides that do not contain disulfide bonds between any of their amino acid residues.

Large gastrin has a molecular weight of around 4 kDa, while small gastrin and mini gastrin have about 2.1 and 1.6 kDa, respectively.

Structure of the «small gastrin» or G-17 (Source: Edgar181 via Wikimedia Commons)

Depending on the conditions of the environment, especially the pH, these molecules of a protein nature can be found as alpha helices or structured as "random coils"

In gastrins G-34 and G-17, the glutamic acid residue located at the N-terminus can "cycle" and prevent the digestion of these peptide hormones by the action of aminopeptidase enzymes.

Production

Gastrin is the active product of the co-translational processing of a precursor molecule: preprogastrin, which in humans has 101 amino acid residues. Preprogastrin is initially processed to produce progastrin, an 80 amino acid peptide.

Progastrin is processed in endocrine cells, first by the enzymes proprotein convertases and then by the enzyme carboxypeptidase E, to give rise to a large gastrin with a C-terminal glycine residue (G34-Gly) or a small gastrin with a residue of C-terminal glycine (G17-Gly).

These molecules remain progastrins as long as they are converted into peptides G-34 and G-17 by "amidation" of the C-terminal end, a process mediated by the action of the enzyme peptidyl alpha-amidating mono-oxygenase (PAM, from English "peptidyl alpha-amidating mono-oxygenase ”).

The endopeptidase-mediated cleavage process and C-terminal amidation occur in the secretory vesicles of G cells.

Structure of the «miniature gastrin» or G-13 (Source: Edgar181 via Wikimedia Commons)

Regulation of its production at the genetic level

Gastrin is encoded by a gene that is typically expressed in G cells of the antral pyloric mucosa and in G cells of the human stomach duodenum. This gene is 4.1 kb and has two introns in its sequence.

Its expression can increase in response to the entry of food into the stomach or it can be inhibited thanks to the presence of acids and the action of somatostatin, which is a hormone responsible for the inhibition of gastrointestinal secretions.

Although not exactly known, it is thought that the cellular signaling pathways that promote the activation of this gene and, therefore, gastrin production, depend on protein kinase enzymes (MAPK pathway).

Secretion

Gastrin secretion depends on certain chemical factors acting on G cells, which are responsible for its synthesis. These factors can have stimulating or inhibitory effects.

G cells come into contact with such chemical factors, either because they are transported through the bloodstream, because they are released from the nerve terminals that are in contact with them, or because they come from the stomach contents that "bathe" the luminal surface of the body. these.

Chemical factors carried in the blood

Although under normal conditions they hardly reach concentrations high enough to promote gastrin release, the "stimulatory" factors that are transported by the bloodstream are epinephrine or adrenaline and calcium.

For example, a significant increase in the transport of calcium to the stomach, which results in the stimulation of gastrin release, is normally associated with conditions such as hyperparathyroidism.

The blood can also carry inhibitory factors, as in the case of other hormonal molecules such as secretin, glucagon and calcitonin.

Chemical factors "luminal" or from food

The food we eat may contain chemical factors that stimulate gastrin secretion, examples of which are calcium and the digestion products of proteins (casein hydrolyzate).

The presence of acidic substances in the stomach lumen has the opposite effect, since it has been reported that these rather inhibit gastrin secretion by affecting all other chemical factors that stimulate its production.

Features

The functions of gastrin are several:

- Stimulates the secretion of enzymes in the stomach, the pancreas and the small intestine.

- Stimulates the secretion of water and electrolytes in the stomach, pancreas, liver, small intestine and Brunner's glands (present in the duodenum).

- Inhibits the absorption of water, glucose and electrolytes in the small intestine.

- Stimulates the smooth muscles of the stomach, small intestine and colon, gallbladder and esophageal sphincter.

- Inhibits the smooth muscles of the pyloric, ileocecal and Oddi sphincters.

- Promotes the release of insulin and calcitonin.

- Increases blood flow to the pancreas, small intestine and stomach.

How does gastrin work?

The action of gastrin is directly related to its interaction with a specific transmembrane receptor protein, known as CCK2R or CCKBR (gastrin receptor).

This receptor has seven transmembrane segments and is coupled to a G protein, which is associated with the cellular signaling pathways of MAP kinases.

Gastritis and other diseases

Gastritis is a pathological condition caused by the gram-negative bacterium Helicobacter pylori that, among the different symptoms, causes a painful inflammation of the stomach lining.

This inflammation caused by H. pylori causes the inhibition of the expression of the hormone somatostatin, which is responsible for inhibiting the production and secretion of gastrin, which translates into a significant increase in the secretion of this hormone and a decrease in stomach pH by exaggerated secretion of gastric acids.

Cancer

Many gastrointestinal tumors are characterized by increased expression of the gene encoding gastrin. Of the most studied, mention can be made of colorectal carcinoma, pancreatic cancer and gastrinoma or Zollinger-Ellison syndrome.

Some of these pathologies may be related to high gastrin gene expression, incorrect processing of precursor peptides, or gene expression at sites other than the stomach.

References

1. Dockray, G., Dimaline, R., & Varro, A. (2005). Gastrin: old hormone, new functions. Eur J Physiol, 449, 344–355.
2. Ferrand, A., & Wang, TC (2006). Gastrin and cancer: A review. Cancer Letters, 238, 15–29.
3. Gregory, H., Hardy, P., D, J., Kenner, G., & Sheppard, R. (1964). The Antral Hormone Gastrin. Nature Publishing Group, 204, 931–933.
4. Jackson, BM, Reeder, DD, & Thompson, JC (1972). Dynamic Characteristics of Gastrin Release. The American Journal of Surgery, 123, 137–142.
5. Walsh, J., & Grossman, M. (1975). Gastrin (First of Two Parts). The New England Journal of Medicine, 292 (25), 1324–1334.