Gastrin

In humans, gastrin is a hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the stomach, duodenum, and the pancreas. Its release is stimulated by gastric luminal peptides. Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool.

Physiology

Genetics

The GAS gene is located on the long arm of the seventeenth chromosome (17q21).

Synthesis

Gastrin is a linear peptide hormone produced by G cells of the duodenum and in the pyloric antrum of the stomach. It is secreted into the bloodstream. Gastrin is found primarily in three forms: gastrin-34 ("big gastrin")
gastrin-17 ("little gastrin")
gastrin-14 ("minigastrin")

Also, pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the C-terminus end of gastrin.

The numbers refer to the amino acid count.

Release

Gastrin is released in response to certain stimuli. These include: stomach distension
vagal stimulation (mediated by the neurocrine bombesin, or GRP in humans)
the presence of partially digested proteins especially amino acids
hypercalcemia

Gastrin release is inhibited by: The presence of acid (primarily the secreted HCl) in the stomach (a case of negative feedback).
Somatostatin also inhibits the release of gastrin, along with secretin, GIP (gastroinhibitory peptide), VIP, glucagon and calcitonin.

Function

The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done indirectly via binding onto CCK2/gastrin receptors on ECL cells in the stomach, which then responds by releasing histamine, which in turn acts in a paracrine manner on parietal cells stimulating them to secrete H+ ions. This is the major stimulus for acid secretion by parietal cells.

Along with the above mentioned function, gastrin has been show to have additional functions as well:

Stimulates parietal cell maturation and fundal growth.
Causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin.
Increases antral muscle mobility and promotes stomach contractions.
Strengthens antral contractions against the pylorus, and constricts the pyloric sphincter, which slows gastric emptying.
Plays a role in the relaxation of the ileocecal valve.
Induces pancreatic secretions and gallbladder emptying.
Impacts lower esophageal sphincter (LES) tone, causing it to relax. Taking this into consideration, high levels of gastrin may play a role in the development of some of the more common LES disorders such as acid reflux disease.

Factors influencing secretion

Gastric lumen: Stimulatory factors: dietary protein and amino acids, hypercalcemia. (i.e. during the gastric phase)
Inhibitory factor: acidity (pH below 3) - a negative feedback mechanism, exerted via the release of somatostatin from δ cells in the stomach, which inhibits gastrin and histamine release.

Paracrine: Stimulatory factor: bombesin
Inhibitory factor: somatostatin - acts on somatostatin-2 receptors on G cells. in a paracrine manner via local diffusion in the intercellular spaces, but also systemically through its release into the local mucosal blood circulation; it inhibits acid secretion by acting on parietal cells.

Nervous: Stimulatory factors: Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP)

Circulation: Stimulatory factor: epinephrine
Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin

Role in disease

In the Zollinger-Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma (gastrin-producing tumor, mostly benign) of the duodenum or the pancreas. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.

In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acidity). This results in an elevated gastrin level in an attempt to compensate for low acidity. Eventually, all the parietal cells are lost and achlorhydria results leading to a loss of negative feedback on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with mucolipidosis type IV (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder.

Translation

The word "Gastrin" occurs as such in the following languages: English, German, Indonesian, Norwegian (Bokmål), Swedish.

Translation(s) in other languages: Divehi: ގެސްޓްރިން, Greek: Γαστρίνη, Spanish: Gastrina, French: Gastrine, Italian: Gastrina, Hebrew: גסטרין, Dutch: Gastrine, Japanese: ガストリン, Polish: Gastryna, Portuguese: Gastrina, Russian: Гастрин, Serbian: Гастрин, Finnish: Gastriini, Chinese: 胃泌素.