Gastrin
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2008-07-08T00:39:25Z
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[[Image:Control-of-stomach-acid-sec.png|thumb|350px|C[[G 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 cell]]s of the [[stomach]], as well as aiding in gastric motility. It is released by [[G cell]]s in the stomach and [[duodenum]]. Its existence was first suggested in 1905 by the British physiologist [[John Sydney Edkins]],<ref>{{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}}</ref><ref>{{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}}</ref> and gastrins were isolated in 1964 by Gregory and Tracy in [[Liverpool]].<ref>{{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}}</ref>
==Physiology==
===Genetics===
The ''GAS'' gene is located on the long arm of the [[seventeenth chromosome]] (17q21).<ref>{{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}}</ref>
===Synthesis===
Gastrin is a linear [[peptide hormone]] produced by [[G cell]]s 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]]
* [[vagus nerve|vagal]] stimulation (mediated by the [[neurocrine]] [[bombesin]], or [[Gastrin releasing peptide|GRP]] in the human)
* the presence of partially [[digestion|digested]] [[protein]]s 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 cell]]s 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 [[gastric chief cell|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 [[pancreas|pancreatic]] enzymes by [[acinar 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 [[delta cell|δ cell]]s 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==
{{reflist}}
==Further reading==
{{refbegin | 2}}
{{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= }}
}}
{{refend}}
==External links==
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gastrin.html Overview at colostate.edu]
* {{GeorgiaPhysiology|6/6ch4/s6ch4_14}}
{{Hormones}}
{{Gastrointestinal physiology}}
{{Gastrointestinal hormones}}
{{Neuropeptides}}
[[Category:Peptide hormones]]
[[Category:Gastric hormones]]
[[Category:Digestive system]]
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