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Gastrin



G cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it.
Gastrin
Identifiers
Symbol GAST
Entrez 2520
HUGO 4164
OMIM 137250
RefSeq NM_000805
UniProt P01350
Other data
Locus Chr. 17 q21

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. Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[1][2] and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool.[3]

Additional recommended knowledge

Contents

Physiology

Genetics

The GAS gene is located on the long arm of the seventeenth chromosome (17q21).[4]

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:

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 ECL cells.

Direct binding of gastrin to the parietal cells is involved in parietal cell maturation and fundul growth.

Gastrin 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:

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.

References

  1. ^ Edkins JS (1906). "The chemical mechanism of gastric secretion". J. Physiol. (Lond.) 34 (1-2): 133–44. PMID 16992839. Full text at PMC: 1465807
  2. ^ Modlin IM, Kidd M, Marks IN, Tang LH (1997). "The pivotal role of John S. Edkins in the discovery of gastrin". World J Surg 21 (2): 226–34. PMID 8995084.
  3. ^ Gregory RA, Tracy HJ (1964). "The constitution and properties of two gastrins extracted from hog antral mucosa". Gut 5: 103–14. PMID 14159395. Full text at PMC: 1552180
  4. ^ Lund T, Geurts van Kessel AH, Haun S, Dixon JE (1986). "The genes for human gastrin and cholecystokinin are located on different chromosomes". Hum. Genet. 73 (1): 77–80. PMID 3011648.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Gastrin". A list of authors is available in Wikipedia.
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