Gastrin Information & Gastrin Links at HealthHaven.com

Gastrin
Identifiers
Symbols	GAST; GAS
External IDs	OMIM: 137250 MGI: 104768 HomoloGene: 628 GeneCards: GAST Gene
Gene ontology
Molecular function	• hormone activity;
Cellular component	• extracellular region; • soluble fraction;
Biological process	• smooth muscle contraction; • signal transduction;
RNA expression pattern
	More reference expression data
Orthologs

edit

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 parietal cells 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]

[edit] Physiology

[edit] Genetics

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

[edit] 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.

[edit] Release

Gastrin is released in response to certain stimuli. These include:

stomach distension
vagal stimulation (mediated by the neurocrine bombesin, or GRP in humans)
the presence of partially digested proteins especially amino acids
hypercalcemia

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, glucagon and calcitonin.

[edit] 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.

[edit] 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:

Stimulatory factor: epinephrine
Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin

[edit] 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 low acidity. 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]

[edit] References

^ 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.
^ 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.
^ 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.
^ 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.
^ 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. PMID 9430795.
^ 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.
^ Castell DO (February 1978). "Gastrin and lower esophageal sphincter tone". Arch. Intern. Med. 138 (2): 196. PMID 626547.
^ 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. PMID 9448310.

[edit] Further reading

Rozengurt E, Walsh JH (2001). "Gastrin, CCK, signaling, and cancer". Annu. Rev. Physiol. 63: 49–76. doi:10.1146/annurev.physiol.63.1.49. PMID 11181948.
Dockray GJ (2005). "Clinical endocrinology and metabolism. Gastrin". Best Pract. Res. Clin. Endocrinol. Metab. 18 (4): 555–68. doi:10.1016/j.beem.2004.07.003. PMID 15533775.
Anlauf M, Garbrecht N, Henopp T, et al. (2006). "Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features". World J. Gastroenterol. 12 (34): 5440–6. PMID 17006979.
Polosatov MV, Klimov PK, Masevich CG, et al. (1979). "Interaction of synthetic human big gastrin with blood proteins of man and animals". Acta hepato-gastroenterologica 26 (2): 154–9. PMID 463490.
Fritsch WP, Hausamen TU, Scholten T (1977). "[Gastrointestinal hormones. I. Hormones of the gastrin group]". Zeitschrift für Gastroenterologie 15 (4): 264–76. PMID 871064.
Higashimoto Y, Himeno S, Shinomura Y, et al. (1989). "Purification and structural determination of urinary NH2-terminal big gastrin fragments". Biochem. Biophys. Res. Commun. 160 (3): 1364–70. doi:10.1016/S0006-291X(89)80154-8. PMID 2730647.
Pauwels S, Najdovski T, Dimaline R, et al. (1989). "Degradation of human gastrin and CCK by endopeptidase 24.11: differential behaviour of the sulphated and unsulphated peptides". Biochim. Biophys. Acta 996 (1-2): 82–8. PMID 2736261.
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.
Kariya Y, Kato K, Hayashizaki Y, et al. (1987). "Expression of human gastrin gene in normal and gastrinoma tissues". Gene 50 (1-3): 345–52. doi:10.1016/0378-1119(86)90338-0. PMID 3034736.
Gregory RA, Tracy HJ, Agarwal KL, Grossman MI (1969). "Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue". Gut 10 (8): 603–8. doi:10.1136/gut.10.8.603. PMID 5822140.
Bentley PH, Kenner GW, Sheppard RC (1967). "Structures of human gastrins I and II". Nature 209 (5023): 583–5. doi:10.1038/209583b0. PMID 5921183.
Ito R, Sato K, Helmer T, et al. (1984). "Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence". Proc. Natl. Acad. Sci. U.S.A. 81 (15): 4662–6. doi:10.1073/pnas.81.15.4662. PMID 6087340.
Wiborg O, Berglund L, Boel E, et al. (1984). "Structure of a human gastrin gene". Proc. Natl. Acad. Sci. U.S.A. 81 (4): 1067–9. doi:10.1073/pnas.81.4.1067. PMID 6322186.
Kato K, Hayashizaki Y, Takahashi Y, et al. (1984). "Molecular cloning of the human gastrin gene". Nucleic Acids Res. 11 (23): 8197–203. doi:10.1093/nar/11.23.8197. PMID 6324077.
Boel E, Vuust J, Norris F, et al. (1983). "Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication". Proc. Natl. Acad. Sci. U.S.A. 80 (10): 2866–9. doi:10.1073/pnas.80.10.2866. PMID 6574456.
Kato K, Himeno S, Takahashi Y, et al. (1984). "Molecular cloning of human gastrin precursor cDNA". Gene 26 (1): 53–7. doi:10.1016/0378-1119(83)90035-5. PMID 6689486.
Koh TJ, Wang TC (1995). "Molecular cloning and sequencing of the murine gastrin gene". Biochem. Biophys. Res. Commun. 216 (1): 34–41. doi:10.1006/bbrc.1995.2588. PMID 7488110.
Rehfeld JF, Hansen CP, Johnsen AH (1995). "Post-poly(Glu) cleavage and degradation modified by O-sulfated tyrosine: a novel post-translational processing mechanism". Embo J. 14 (2): 389–96. PMID 7530658.
Rehfeld JF, Johnsen AH (1994). "Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product". Eur. J. Biochem. 223 (3): 765–73. doi:10.1111/j.1432-1033.1994.tb19051.x. PMID 8055952.
Varro A, Dockray GJ (1993). "Post-translational processing of progastrin: inhibition of cleavage, phosphorylation and sulphation by brefeldin A". Biochem. J. 295 ( Pt 3): 813–9. PMID 8240296.

[edit] External links

[0] 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.

[1] 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.

[2] 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.

[3] 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.

[pmid9430795-4] 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. PMID 9430795.

[pmid950091-5] 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.

[pmid626547-6] Castell DO (February 1978). "Gastrin and lower esophageal sphincter tone". Arch. Intern. Med. 138 (2): 196. PMID 626547.

[pmid9448310-7] 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. PMID 9448310.

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