Gastrin

In humans, gastrin is a hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach, as well as aiding in gastric motility. 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, [cite journal |author=Edkins JS |title=The chemical mechanism of gastric secretion |journal=J. Physiol. (Lond.) |volume=34 |issue=1-2 |pages=133–44 |year=1906 |pmid=16992839 |url=http://jp.physoc.org/cgi/reprint/34/1-2/133 | pmc=1465807] [cite journal |author=Modlin IM, Kidd M, Marks IN, Tang LH |title=The pivotal role of John S. Edkins in the discovery of gastrin |journal=World J Surg |volume=21 |issue=2 |pages=226–34 |year=1997 |pmid=8995084 |doi=10.1007/s002689900221] and gastrins were isolated in 1964 by Gregory and Tracy in Liverpool. [cite journal |author=Gregory RA, Tracy HJ |title=The constitution and properties of two gastrins extracted from hog antral mucosa |journal=Gut |volume=5 |issue= |pages=103–14 |year=1964 |pmid=14159395 |url=http://gut.bmj.com/cgi/reprint/5/2/103 |doi=10.1136/gut.5.2.103 | pmc=1552180]

Physiology

Genetics

The "GAS" gene is located on the long arm of the seventeenth chromosome (17q21). [cite journal |author=Lund T, Geurts van Kessel AH, Haun S, Dixon JE |title=The genes for human gastrin and cholecystokinin are located on different chromosomes |journal=Hum. Genet. |volume=73 |issue=1 |pages=77–80 |year=1986 |pmid=3011648 |doi=10.1007/BF00292669]

ynthesis

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:
* 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.

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 fundal 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. In digestion, gastrin strengthens the antral contractions against the pylorus, and constricts the pyloric sphincter, which has the effect of slowing the rate of gastric emptying.

Gastrin has also been shown to induce production of pancreatic enzymes by centroacinar 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:
* Stimulatory factor: epinephrine
* Inhibitory factors:gastric inhibitory peptide (GIP), secretin, somatostatin, glucagon, calcitonin

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 pyloric 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 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.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Rozengurt E, Walsh JH |title=Gastrin, CCK, signaling, and cancer |journal=Annu. Rev. Physiol. |volume=63 |issue= |pages= 49–76 |year= 2001 |pmid= 11181948 |doi= 10.1146/annurev.physiol.63.1.49
*cite journal | author=Dockray GJ |title=Clinical endocrinology and metabolism. Gastrin |journal=Best Pract. Res. Clin. Endocrinol. Metab. |volume=18 |issue= 4 |pages= 555–68 |year= 2005 |pmid= 15533775 |doi= 10.1016/j.beem.2004.07.003
*cite journal | author=Anlauf M, Garbrecht N, Henopp T, "et al." |title=Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features |journal=World J. Gastroenterol. |volume=12 |issue= 34 |pages= 5440–6 |year= 2006 |pmid= 17006979 |doi=
*cite journal | author=Polosatov MV, Klimov PK, Masevich CG, "et al." |title=Interaction of synthetic human big gastrin with blood proteins of man and animals |journal=Acta hepato-gastroenterologica |volume=26 |issue= 2 |pages= 154–9 |year= 1979 |pmid= 463490 |doi=
*cite journal | author=Fritsch WP, Hausamen TU, Scholten T |title= [Gastrointestinal hormones. I. Hormones of the gastrin group] |journal=Zeitschrift für Gastroenterologie |volume=15 |issue= 4 |pages= 264–76 |year= 1977 |pmid= 871064 |doi=
*cite journal | author=Higashimoto Y, Himeno S, Shinomura Y, "et al." |title=Purification and structural determination of urinary NH2-terminal big gastrin fragments |journal=Biochem. Biophys. Res. Commun. |volume=160 |issue= 3 |pages= 1364–70 |year= 1989 |pmid= 2730647| doi=10.1016/S0006-291X(89)80154-8
*cite journal | author=Pauwels S, Najdovski T, Dimaline R, "et al." |title=Degradation of human gastrin and CCK by endopeptidase 24.11: differential behaviour of the sulphated and unsulphated peptides |journal=Biochim. Biophys. Acta |volume=996 |issue= 1-2 |pages= 82–8 |year= 1989 |pmid= 2736261 |doi=
*cite journal | author=Lund T, Geurts van Kessel AH, Haun S, Dixon JE |title=The genes for human gastrin and cholecystokinin are located on different chromosomes |journal=Hum. Genet. |volume=73 |issue= 1 |pages= 77–80 |year= 1986 |pmid= 3011648| doi=10.1007/BF00292669
*cite journal | author=Kariya Y, Kato K, Hayashizaki Y, "et al." |title=Expression of human gastrin gene in normal and gastrinoma tissues |journal=Gene |volume=50 |issue= 1-3 |pages= 345–52 |year= 1987 |pmid= 3034736 |doi=
*cite journal | author=Gregory RA, Tracy HJ, Agarwal KL, Grossman MI |title=Aminoacid constitution of two gastrins isolated from Zollinger-Ellison tumour tissue |journal=Gut |volume=10 |issue= 8 |pages= 603–8 |year= 1969 |pmid= 5822140| doi=10.1136/gut.10.8.603
*cite journal | author=Bentley PH, Kenner GW, Sheppard RC |title=Structures of human gastrins I and II |journal=Nature |volume=209 |issue= 5023 |pages= 583–5 |year= 1967 |pmid= 5921183 |doi=
*cite journal | author=Ito R, Sato K, Helmer T, "et al." |title=Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=81 |issue= 15 |pages= 4662–6 |year= 1984 |pmid= 6087340| doi=10.1073/pnas.81.15.4662
*cite journal | author=Wiborg O, Berglund L, Boel E, "et al." |title=Structure of a human gastrin gene |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=81 |issue= 4 |pages= 1067–9 |year= 1984 |pmid= 6322186| doi=10.1073/pnas.81.4.1067
*cite journal | author=Kato K, Hayashizaki Y, Takahashi Y, "et al." |title=Molecular cloning of the human gastrin gene |journal=Nucleic Acids Res. |volume=11 |issue= 23 |pages= 8197–203 |year= 1984 |pmid= 6324077 |doi=
*cite journal | author=Boel E, Vuust J, Norris F, "et al." |title=Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 10 |pages= 2866–9 |year= 1983 |pmid= 6574456| doi=10.1073/pnas.80.10.2866
*cite journal | author=Kato K, Himeno S, Takahashi Y, "et al." |title=Molecular cloning of human gastrin precursor cDNA |journal=Gene |volume=26 |issue= 1 |pages= 53–7 |year= 1984 |pmid= 6689486 |doi=
*cite journal | author=Koh TJ, Wang TC |title=Molecular cloning and sequencing of the murine gastrin gene |journal=Biochem. Biophys. Res. Commun. |volume=216 |issue= 1 |pages= 34–41 |year= 1995 |pmid= 7488110 |doi= 10.1006/bbrc.1995.2588
*cite journal | author=Rehfeld JF, Hansen CP, Johnsen AH |title=Post-poly(Glu) cleavage and degradation modified by O-sulfated tyrosine: a novel post-translational processing mechanism |journal=EMBO J. |volume=14 |issue= 2 |pages= 389–96 |year= 1995 |pmid= 7530658 |doi=
*cite journal | author=Rehfeld JF, Johnsen AH |title=Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product |journal=Eur. J. Biochem. |volume=223 |issue= 3 |pages= 765–73 |year= 1994 |pmid= 8055952| doi=10.1111/j.1432-1033.1994.tb19051.x
*cite journal | author=Varro A, Dockray GJ |title=Post-translational processing of progastrin: inhibition of cleavage, phosphorylation and sulphation by brefeldin A |journal=Biochem. J. |volume=295 ( Pt 3) |issue= |pages= 813–9 |year= 1993 |pmid= 8240296 |doi=

External links

* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gastrin.html Overview at colostate.edu]
*

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes