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In humans, 'gastrin' is a hormone that stimulates secretion of gastric acid by the parietal cells of the stomach. It is released by G cells in the stomach and duodenum.

Contents

Physiology

Genetics

Synthesis

Release

Function

Factors influencing secretion

Role in disease

External links

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")
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 the human)

★ 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, 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 either directly or indirectly:

★ ''Directly:'' binds onto CCK2/gastrin receptors on parietal cells stimulating them to secrete H+ ions.

★ ''Indirectly:'' binds 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 ECL cells.
It also causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin. Pepsinogen is converted to pepsin in a low pH environment, and the HCl provides a suitable environment for its activity.
It can also increase antral muscle mobility and trophic effect on GI tract and causes promotion of contraction of circular muscle of the stomach.
Gastrin has also been shown to induce production of pancreatic enzymes by acinar cells.
It increases gastric blood flow.

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 antrum 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 hypochlorhydia (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.

External links

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★ Overview at colostate.edu

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