Gastrin: Wikis

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Gastrin
Identifiers
Symbols GAST; GAS
External IDs OMIM137250 MGI104768 HomoloGene628 GeneCards: GAST Gene
RNA expression pattern
PBB GE GAST 208138 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2520 14459
Ensembl ENSG00000184502 ENSMUSG00000017165
UniProt P01350 Q6GSF5
RefSeq (mRNA) NM_000805 NM_010257
RefSeq (protein) NP_000796 NP_034387
Location (UCSC) Chr 17:
37.12 - 37.13 Mb
Chr 11:
100.15 - 100.15 Mb
PubMed search [1] [2]
CG cell is visible near bottom left, and gastrin is labeled as the two black arrows leading from it.

In humans, gastrin is a hormone that stimulates secretion of gastric acid (HCl) by the G cells s 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,[1][2] and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool.[3]

Contents

Physiology

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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:

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:

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 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.[5]
  • Induces pancreatic secretions and gallbladder emptying.[6]
  • Impacts lower esophageal sphincter (LES) tone, causing it to relax.[7] 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:

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 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.[8]

References

  1. ^ Edkins JS (13 March 1906). "The chemical mechanism of gastric secretion". J. Physiol. (Lond.) 34 (1-2): 133–44. PMID 16992839.& PMC 1465807. http://jp.physoc.org/cgi/reprint/34/1-2/133. 
  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. doi:10.1007/s002689900221. PMID 8995084. 
  3. ^ Gregory RA, Tracy HJ (1964). "The constitution and properties of two gastrins extracted from hog antral mucosa". Gut 5: 103–14. doi:10.1136/gut.5.2.103. PMID 14159395.& PMC 1552180. http://gut.bmj.com/cgi/reprint/5/2/103. 
  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. doi:10.1007/BF00292669. PMID 3011648. 
  5. ^ Vadokas B, Lüdtke FE, Lepsien G, Golenhofen K, Mandrek K (December 1997). "Effects of gastrin-releasing peptide (GRP) on the mechanical activity of the human ileocaecal region in vitro". Neurogastroenterol Motil. 9 (4): 265–270. doi:10.1046/j.1365-2982.1997.d01-59.x. PMID 9430795. 
  6. ^ Valenzuela JE, Walsh JH, Isenberg JI (September 1976). "Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man". Gastroenterology 71 (3): 409–411. PMID 950091. 
  7. ^ Castell DO (February 1978). "Gastrin and lower esophageal sphincter tone". Arch. Intern. Med. 138 (2): 196. doi:10.1001/archinte.138.2.196. PMID 626547. 
  8. ^ Schiffmann R, Dwyer NK, Lubensky IA, Tsokos M, Sutliff VE, Latimer JS, Frei KP, Brady RO, Barton NW, Blanchette-Mackie EJ, Goldin E (February 1998). "Constitutive achlorhydria in mucolipidosis type IV". Proc Natl Acad Sci U S A. 95 (3): 1207–12. doi:10.1073/pnas.95.3.1207. PMID 9448310. 

Further reading

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