Gastrin

Gastrin
Identifiers
Symbols	GAST ; GAS
External IDs	OMIM: 137250 MGI: 1098667 HomoloGene: 628 GeneCards: GAST Gene
Gene ontology Molecular function • hormone activity • protein binding Cellular component • extracellular region • extracellular space Biological process • signal transduction • G-protein coupled receptor signaling pathway • response to food Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2520	14459
Ensembl	ENSG00000184502	ENSMUSG00000017165
UniProt	P01350	P48757
RefSeq (mRNA)	NM_000805	NM_010257
RefSeq (protein)	NP_000796	NP_034387
Location (UCSC)	Chr 17: 41.71 – 41.72 Mb	Chr 11: 100.33 – 100.34 Mb
PubMed search	[1]	[2]

Gastrin
Identifiers
Symbol	Gastrin
Pfam	PF00918
InterPro	IPR001651
PROSITE	PDOC00232
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Gastrin is a peptide 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 pyloric antrum of the stomach, duodenum, and the pancreas.

Gastrin binds to 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 peptides in the lumen of the stomach.

Physiology

Genetics

The GAS gene is located on the long arm of the eighteenth 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 antrum distension
• vagal stimulation (mediated by the neurocrine bombesin, or GRP in humans)
• the presence of partially digested proteins, especially amino acids, in the stomach
• hypercalcemia (via Calcium-sensing receptors)

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 (vasoactive intestinal peptide), glucagon and calcitonin.

Function

G cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it. Note: this diagram does not illustrate gastrin's stimulatory effect on ECL cells.

The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid. This is done both directly on the parietal cell and 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 shown 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 diminishes the rate of gastric emptying.
• Plays a role in the relaxation of the ileocecal valve.
• Induces pancreatic secretions and gallbladder emptying.
• May impact lower esophageal sphincter (LES) tone, causing it to contract, - although pentagastrin, rather than endogenous gastrin, may be the cause.

Factors influencing secretion

Gastric lumen

• Stimulatory factors: dietary protein and amino acids (meat), 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)
• Inhibitory factor: Enterogastric reflex

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 increased pH in the stomach. 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.

History

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

External links

• Overview at colostate.edu
• Physiology: 6/6ch4/s6ch4_14 - Essentials of Human Physiology