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Gastrin

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GAST
Identifiers
AliasesGAST, GAS, gastrin
External IDsOMIM: 137250; MGI: 104768; HomoloGene: 628; GeneCards: GAST; OMA:GAST - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 11: 100.23 – 100.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Gastrin
Identifiers
SymbolGastrin
PfamPF00918
InterProIPR001651
PROSITEPDOC00232
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure 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 seventeenth chromosome (17q21).[5]

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: [citation needed]

Gastrin release is inhibited by:[7][8]

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. [citation needed]

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.[9]
  • Induces pancreatic secretions and gallbladder emptying.[10]
  • May impact lower esophageal sphincter (LES) tone, causing it to contract,[11] - although pentagastrin, rather than endogenous gastrin, may be the cause.[12]

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

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. [citation needed]

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.[13]

History

Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[14][15] and gastrins were isolated in 1964 by Roderic Alfred Gregory at the University of Liverpool.[16] In 1964 the structure of Gastrin was determined.[17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000184502 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017165 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR, Wank SA (2010). "Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion". Proc. Natl. Acad. Sci. U.S.A. 107 (41): 17791–17796. doi:10.1073/pnas.1009078107. PMID 20876097.
  7. ^ Holst JJ, Orskov C, Seier-Poulsen S (1992). "Somatostatin is an essential paracrine link in acid inhibition of gastrin secretion". Digestion. 51 (2): 95–102. doi:10.1159/000200882. PMID 1354190.
  8. ^ Johnson LR (1984). "Effects of somatostatin and acid on inhibition of gastrin release in newborn rats". Endocrinology. 114 (3): 743–746. doi:10.1210/endo-114-3-743. PMID 6141932.
  9. ^ Vadokas B, Lüdtke FE, Lepsien G, Golenhofen K, Mandrek K (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.
  10. ^ Valenzuela JE, Walsh JH, Isenberg JI (1976). "Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man". Gastroenterology. 71 (3): 409–411. PMID 950091.
  11. ^ Castell DO (1978). "Gastrin and lower esophageal sphincter tone". Arch. Intern. Med. 138 (2): 196. doi:10.1001/archinte.138.2.196. PMID 626547.
  12. ^ Henderson JM, Lidgard G, Osborne DH, Carter DC, Heading RC (1978). "Lower oesophageal sphincter response to gastrin--pharmacological or physiological?". Gut. 19 (2): 99–102. doi:10.1136/gut.19.2.99. PMC 1411818. PMID 631634.
  13. ^ Schiffmann R, Dwyer NK, Lubensky IA, Tsokos M, Sutliff VE, Latimer JS, Frei KP, Brady RO, Barton NW, Blanchette-Mackie EJ, Goldin E (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. PMC 18720. PMID 9448310.
  14. ^ Edkins JS (1906). "The chemical mechanism of gastric secretion". J. Physiol. (Lond.). 34 (1–2): 133–44. PMC 1465807. PMID 16992839.
  15. ^ 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.
  16. ^ Gregory RA, Tracy HJ (1964). "The constitution and properties of two gastrins extracted from hog antral mucosa: Part I the isolation of two gastrins from hog antral mucosa". Gut. 5 (2): 103–107. doi:10.1136/gut.5.2.103.
  17. ^ Gregory H, Hardy PM, Jones DS, Kenner GW, Sheppard RC (1964). "THE ANTRAL HORMONE GASTRIN. STRUCTURE OF GASTRIN". Nature. 204: 931–3. doi:10.1038/204931a0. PMID 14248711.

Further reading

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