Gastrin

Gastrin is a is_associated_with::peptide hormone that stimulates secretion of is_associated_with::gastric acid (HCl) by the is_associated_with::parietal cells of the is_associated_with::stomach and aids in gastric motility. It is released by is_associated_with::G cells in the is_associated_with::pyloric antrum of the stomach, is_associated_with::duodenum, and the is_associated_with::pancreas.

Gastrin binds to is_associated_with::cholecystokinin B receptors to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ ATPase pumps into the apical membrane of parietal cells (which in turn increases H+ release into the stomach cavity). Its release is stimulated by is_associated_with::peptides in the lumen of the stomach.

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

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

Also, is_associated_with::pentagastrin is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the is_associated_with::C-terminus end of gastrin. The numbers refer to the is_associated_with::amino acid count.

Release
Gastrin is released in response to certain stimuli. These include:
 * is_associated_with::Stomach antrum distension
 * vagal stimulation (mediated by the neurocrine is_associated_with::bombesin, or GRP in humans)
 * the presence of partially digested is_associated_with::proteins, especially is_associated_with::amino acids
 * is_associated_with::hypercalcemia (via is_associated_with::Calcium-sensing receptors )

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

Function


The presence of gastrin stimulates is_associated_with::parietal cells of the stomach to is_associated_with::secrete is_associated_with::hydrochloric acid (HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding onto CCK2/gastrin receptors on is_associated_with::ECL cells in the stomach, which then responds by releasing is_associated_with::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 shown to have additional functions as well:


 * Stimulates parietal cell maturation and fundal growth.
 * Causes chief cells to secrete is_associated_with::pepsinogen, the is_associated_with::zymogen (inactive) form of the digestive is_associated_with::enzyme is_associated_with::pepsin.
 * Increases antral muscle mobility and promotes stomach contractions.
 * Strengthens antral contractions against the pylorus, and constricts the pyloric sphincter, which diminishes the rate of gastric emptying.
 * Plays a role in the relaxation of the is_associated_with::ileocecal valve.
 * Induces pancreatic secretions and is_associated_with::gallbladder emptying.
 * May impact is_associated_with::lower esophageal sphincter (LES) tone, causing it to contract, - although pentagastrin, rather than endogenous gastrin, may be the cause.

Gastric lumen

 * Stimulatory factors: dietary protein and amino acids (meat), is_associated_with::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: is_associated_with::bombesin
 * Inhibitory factor: is_associated_with::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: is_associated_with::Beta-adrenergic agents, is_associated_with::cholinergic agents, is_associated_with::gastrin-releasing peptide (GRP)
 * Inhibitory factor: is_associated_with::Enterogastric reflex

Circulation

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

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

In autoimmune is_associated_with::gastritis, the immune system attacks the is_associated_with::parietal cells leading to is_associated_with::hypochlorhydria (low stomach acidity). This results in an elevated gastrin level in an attempt to compensate for increased pH in the stomach. Eventually, all the parietal cells are lost and is_associated_with::achlorhydria results leading to a loss of is_associated_with::negative feedback on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with is_associated_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.

History
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by is_associated_with::Roderic Alfred Gregory at the is_associated_with::University of Liverpool. In 1964 the structure of Gastrin was determined.