In humans, gastrin is a
hormonethat 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]
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]
Gastrin is a linear
peptide hormoneproduced by G cells of the duodenum and in the pyloric antrumof 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
Gastrin is released in response to certain stimuli. These include:
* vagal stimulation (mediated by the
neurocrine bombesin, or GRP in the human)
* the presence of partially digested
proteins especially amino acids
Gastrin release is inhibited by:
* The presence of
acid(primarily the secreted HCl) in the stomach (a case of negative feedback).
Somatostatinalso inhibits the release of gastrin, along with secretin, GIP( gastroinhibitory peptide), VIP, glucagonand calcitonin.
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 cellsin 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 pHenvironment, 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
* 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.
* Stimulatory factor:
* 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.
* Stimulatory factors:
Beta-adrenergicagents, cholinergicagents, gastrin-releasing peptide(GRP) Circulation:
* Stimulatory factor:
* Inhibitory factors:
gastric inhibitory peptide(GIP), secretin, somatostatin, glucagon, calcitonin
Role in disease
Zollinger-Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma(gastrin-producing tumor, mostly benign) of the pyloric antrumor the pancreas. To investigate for hypergastrinemia (high blood levels of gastrin), a "pentagastrin test" can be performed.
gastritis, the immune system attacks the parietal cellsleading 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 achlorhydriaresults leading to a loss of negative feedbackon gastrin secretion.
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* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gastrin.html Overview at colostate.edu]
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