Gastrin

Gastrin
Identifiers
Symbols GAST ; GAS
External IDs OMIM: 137250 MGI: 1098667 HomoloGene: 628 GeneCards: GAST Gene
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
Gastrin
Identifiers
Symbol Gastrin
Pfam PF00918
InterPro IPR001651
PROSITE PDOC00232

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).[1]

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:[3][4]

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:

Factors influencing secretion

Gastric lumen

Paracrine

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.[9]

History

Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[10][11] and gastrins were isolated in 1964 by Roderic Alfred Gregory at the University of Liverpool.[12] In 1964 the structure of Gastrin was determined.[13]

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Castell DO (1978). "Gastrin and lower esophageal sphincter tone". Arch. Intern. Med. 138 (2): 196. doi:10.1001/archinte.138.2.196. PMID 626547.
  8. 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.
  9. 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.
  10. Edkins JS (1906). "The chemical mechanism of gastric secretion". J. Physiol. (Lond.) 34 (1-2): 133–44. PMC 1465807. PMID 16992839.
  11. 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.
  12. 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.
  13. 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

External links

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