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{{GS}}
{{Infobox_gene}}
 
{{Infobox protein family
 
| Symbol = Gastrin
 
| Name = Gastrin
==Overview==
| image =  
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| update_protein_box = yes
| InterPro = IPR001651
| update_summary = no
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| PROSITE = PDOC00232
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
'''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 cell]]s in the [[pyloric antrum]] of the stomach, [[duodenum]], and the [[pancreas]].
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Gastrin
| HGNCid = 4164
| Symbol = GAST
| AltSymbols =; GAS
| OMIM = 137250
| ECnumber = 
| Homologene = 628
| MGIid = 104768
| GeneAtlas_image1 = PBB_GE_GAST_208138_at_tn.png
| Function = {{GNF_GO|id=GO:0005179 |text = hormone activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005625 |text = soluble fraction}}
| Process = {{GNF_GO|id=GO:0006939 |text = smooth muscle contraction}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2520
    | Hs_Ensembl = ENSG00000184502
    | Hs_RefseqProtein = NP_000796
    | Hs_RefseqmRNA = NM_000805
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 37122139
    | Hs_GenLoc_end = 37125746
    | Hs_Uniprot = P01350
    | Mm_EntrezGene = 14459
    | Mm_Ensembl = ENSMUSG00000017165
    | Mm_RefseqmRNA = NM_010257
    | Mm_RefseqProtein = NP_034387
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 100150497
    | Mm_GenLoc_end = 100153086
    | Mm_Uniprot = Q6GSF5
  }}
}}
__NOTOC__
{{SI}}


In humans, '''gastrin''' is a [[hormone]] that stimulates secretion of [[gastric acid]] by the [[parietal cell]]s of the [[stomach]]. 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=}}</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}} {{PMC|1552180}}</ref>
Gastrin binds to [[cholecystokinin B receptor]]s to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K<sup>+</sup>/H<sup>+</sup> ATPase pumps into the apical membrane of parietal cells (which in turn increases H<sup>+</sup> release into the stomach cavity). Its release is stimulated by [[peptides]] in the [[Lumen (anatomy)|lumen]] of the stomach.


==Physiology==
==Physiology==
===Genetics===
===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=}}</ref>
 
In humans, the ''GAS'' gene is located on the long arm of the [[seventeenth chromosome]] (17q21).<ref>{{cite journal | vauthors = Lund T, Geurts van Kessel AH, Haun S, Dixon JE | title = The genes for human gastrin and cholecystokinin are located on different chromosomes | journal = Human Genetics | volume = 73 | issue = 1 | pages = 77–80 | date = May 1986 | pmid = 3011648 | doi = 10.1007/BF00292669 }}</ref>


===Synthesis===
===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 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. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in [[posttranslational modification]] to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:  
* ''gastrin-34'' ("big gastrin")
* ''[[gastrin-34]]'' ("[[big gastrin]]")
* ''gastrin-17'' ("little gastrin")
* ''[[gastrin-17]]'' ("[[little gastrin]]")
* ''gastrin-14'' ("minigastrin")  
* ''[[gastrin-14]]'' ("[[minigastrin]]")


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.
The numbers refer to the [[amino acid]] count.


===Release===
===Release===
Gastrin is released in response to certain stimuli.  These include: {{Citation needed|date=July 2013}}
* [[stomach antrum]] distension
* [[vagus nerve|vagal]] stimulation (mediated by the [[Cell signaling|neurocrine]] [[bombesin]], or [[Gastrin releasing peptide|GRP]] in humans)
* the presence of partially [[digestion|digested]] [[protein]]s, especially [[amino acids]], in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.<ref>{{Citation|last=Blanco|first=Antonio|title=Biochemical Bases of Endocrinology (II) Hormones and Other Chemical Intermediates|date=2017|url=http://dx.doi.org/10.1016/b978-0-12-803550-4.00026-4|work=Medical Biochemistry|pages=573–644|publisher=Elsevier|isbn=9780128035504|access-date=2018-11-02|last2=Blanco|first2=Gustavo}}</ref>
* [[hypercalcemia]] (via [[calcium-sensing receptor]]s<ref>{{cite journal | vauthors = Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR, Wank SA | title = Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 41 | pages = 17791–6 | date = October 2010 | pmid = 20876097 | doi = 10.1073/pnas.1009078107 | pmc=2955134}}</ref>)


Gastrin is released in response to certain stimuli. These include:  
Gastrin release is inhibited by:<ref>{{cite journal | vauthors = Holst JJ, Orskov C, Seier-Poulsen S | title = Somatostatin is an essential paracrine link in acid inhibition of gastrin secretion | journal = Digestion | volume = 51 | issue = 2 | pages = 95–102 | year = 1992 | pmid = 1354190 | doi = 10.1159/000200882 }}</ref><ref>{{cite journal | vauthors = Johnson LR | title = Effects of somatostatin and acid on inhibition of gastrin release in newborn rats | journal = Endocrinology | volume = 114 | issue = 3 | pages = 743–6 | date = March 1984 | pmid = 6141932 | doi = 10.1210/endo-114-3-743 | url = http://endo.endojournals.org/cgi/content/abstract/114/3/743 }}</ref>
* stomach [[distension]]
* the presence of [[acid]] (primarily the secreted HCl) in the stomach (a case of [[negative feedback]]) 
* [[vagus nerve|vagal]] stimulation (mediated by the [[neurocrine]] [[bombesin]], or [[Gastrin releasing peptide|GRP]] in the human)
* [[somatostatin]] also inhibits the release of gastrin, along with [[secretin]], GIP ([[gastroinhibitory peptide]]), VIP ([[vasoactive intestinal peptide]]), [[glucagon]] and [[calcitonin]].
* the presence of partially [[digestion|digested]] [[protein]]s especially [[amino acids]]
* [[hypercalcemia]]


[[image:Control-of-stomach-acid-sec.png|thumb|center|350px]]
=== Function ===
[[Image:Control-of-stomach-acid-sec.png|thumb|350px|[[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.]]


Gastrin release is inhibited by:
The presence of gastrin stimulates [[parietal cell]]s of the stomach to [[secrete]] [[hydrochloric acid]] (HCl)/gastric acid.  This is done both directly on the parietal cell and indirectly via binding onto [[Cholecystokinin B receptor|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 [[Hydron (chemistry)|H+ ion]]s. This is the major stimulus for acid secretion by parietal cells. {{Citation needed|date=July 2013}}
* 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, VIP, [[glucagon]] and [[calcitonin]].


===Function===
Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
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 fundul growth.
* Stimulates parietal cell maturation and fundal growth.
* Causes [[gastric chief cell|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 relaxes the pyloric sphincter, which increases the rate of gastric emptying.<ref>Tortora, G. J., & Grabowski, S. R. (1996). Principles of anatomy and physiology. New York, NY: HarperCollins College. 14th Ed. Pg 906</ref>
* Plays a role in the relaxation of the [[ileocecal valve]].<ref name="pmid9430795">{{cite journal | vauthors = Vadokas B, Lüdtke FE, Lepsien G, Golenhofen K, Mandrek K | title = Effects of gastrin-releasing peptide (GRP) on the mechanical activity of the human ileocaecal region in vitro | journal = Neurogastroenterology and Motility | volume = 9 | issue = 4 | pages = 265–70 | date = December 1997 | pmid = 9430795 | doi = 10.1046/j.1365-2982.1997.d01-59.x }}</ref>
* Induces [[pancreas|pancreatic]] secretions and [[gallbladder]] emptying.<ref name="pmid950091">{{cite journal | vauthors = Valenzuela JE, Walsh JH, Isenberg JI | title = Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man | journal = Gastroenterology | volume = 71 | issue = 3 | pages = 409–11 | date = September 1976 | pmid = 950091 | doi =  }}</ref>
* May impact [[lower esophageal sphincter]] (LES) tone, causing it to contract,<ref name="pmid626547">{{cite journal | vauthors = Castell DO | title = Gastrin and lower esophageal sphincter tone | journal = Archives of Internal Medicine | volume = 138 | issue = 2 | pages = 196 | date = February 1978 | pmid = 626547 | doi = 10.1001/archinte.138.2.196 }}</ref> - although pentagastrin, rather than endogenous gastrin, may be the cause.<ref name="pmid631634">{{cite journal | vauthors = Henderson JM, Lidgard G, Osborne DH, Carter DC, Heading RC | title = Lower oesophageal sphincter response to gastrin--pharmacological or physiological? | journal = Gut | volume = 19 | issue = 2 | pages = 99–102 | date = February 1978 | pmid = 631634 | pmc = 1411818 | doi = 10.1136/gut.19.2.99 }}</ref>
* Gastrin contributes to the [[gastrocolic reflex]].


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.
===Factors influencing secretion===
It can also increase antral muscle mobility and trophic effect on GI tract and causes promotion of contraction of circular muscle of the stomach.
{{More citations needed|date=April 2014}}


Gastrin has also been shown to induce production of [[pancreas|pancreatic]] enzymes by [[acinar cells]].
====Physiologic====
 
=====Gastric lumen=====
It increases gastric blood flow.
* Stimulatory factors: dietary protein and amino acids (meat), [[hypercalcemia]]. (i.e. during the gastric phase)
 
===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.
* 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:
=====Paracrine=====
* Stimulatory factor: [[bombesin]]
* Stimulatory factor: [[bombesin]] or [[gastrin-releasing peptide]] (GRP)
* 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.
* 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:
=====Nervous=====
* Stimulatory factors: [[Beta-adrenergic]] agents, [[cholinergic]] agents, [[gastrin-releasing peptide]] (GRP)
* Stimulatory factors: [[Beta-adrenergic]] agents, [[cholinergic]] agents, [[gastrin-releasing peptide]] (GRP)
         
* Inhibitory factor: [[Enterogastric reflex]]
Circulation:
 
=====Circulation=====
* Stimulatory factor: [[epinephrine]]
* Stimulatory factor: [[epinephrine]]
* Inhibitory factors:[[gastric inhibitory peptide]] (GIP), [[secretin]], [[somatostatin]], [[glucagon]], [[calcitonin]]
* Inhibitory factors:[[gastric inhibitory peptide]] (GIP), [[secretin]], [[somatostatin]], [[glucagon]], [[calcitonin]]
====Pathophysiologic====
=====Paraneoplastic=====
* Gastrinoma [[paraneoplastic syndrome|paraneoplastic]] oversecretion (see ''[[#Role in disease|Role in disease]]'')


== Role in disease ==
== 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 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. {{Citation needed|date=July 2013}}


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.
In autoimmune [[gastritis]], the immune system attacks the [[parietal cells]] leading to [[hypochlorhydria]] (low stomach acid secretion).  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.<ref name="pmid9448310">{{cite journal | vauthors = Schiffmann R, Dwyer NK, Lubensky IA, Tsokos M, Sutliff VE, Latimer JS, Frei KP, Brady RO, Barton NW, Blanchette-Mackie EJ, Goldin E | title = Constitutive achlorhydria in mucolipidosis type IV | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 3 | pages = 1207–12 | date = February 1998 | pmid = 9448310 | pmc = 18720 | doi = 10.1073/pnas.95.3.1207 }}</ref> Additionally, elevated gastrin levels may be present in chronic gastritis resulting from ''H pylori'' infection.<ref>{{cite web|title=Review Article: Strategies to Determine Whether Hypergastrinaemia Is Due to Zollinger-Ellison Syndrome Rather Than a More Common Benign Cause|url=http://www.medscape.com/viewarticle/703619_5|website=www.medscape.com}}</ref>


==References==
==History==
<references/>
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,<ref>{{cite journal | vauthors = Edkins JS | title = The chemical mechanism of gastric secretion | journal = The Journal of Physiology | volume = 34 | issue = 1–2 | pages = 133–44 | date = March 1906 | pmid = 16992839 | pmc = 1465807 | url = http://jp.physoc.org/cgi/reprint/34/1-2/133 | doi=10.1113/jphysiol.1906.sp001146}}</ref><ref>{{cite journal | vauthors = Modlin IM, Kidd M, Marks IN, Tang LH | title = The pivotal role of John S. Edkins in the discovery of gastrin | journal = World Journal of Surgery | volume = 21 | issue = 2 | pages = 226–34 | date = February 1997 | pmid = 8995084 | doi = 10.1007/s002689900221 }}</ref> and gastrins were isolated in 1964 by [[Hilda J. Tracy]] and [[Roderic Alfred Gregory]] at the [[University of Liverpool]].<ref>{{cite journal | vauthors = Gregory RA, Tracy HJ | title = The constitution and properties of two gastrins extracted from hog antral mucosa: Part I the isolation of two gastrins from hog antral mucosa | journal = Gut | volume = 5 | issue = 2 | pages = 103–107 | year = 1964 | pmid =  | pmc =  1552180| doi = 10.1136/gut.5.2.103 | authorlink1 = Roderic Alfred Gregory }}</ref> In 1964 the structure of gastrin was determined.<ref name="pmid14248711">{{cite journal | vauthors = Gregory H, Hardy PM, Jones DS, Kenner GW, Sheppard RC | title = The antral hormone gastrin. Structure of gastrin. | journal = Nature | volume = 204 | issue =  | pages = 931–3 | date = December 1964 | pmid = 14248711 | doi = 10.1038/204931a0 }}</ref>


==External links==
== References ==
{{Reflist|33em}}
 
== Further reading ==
{{Refbegin|33em}}
* {{cite journal | vauthors = Rozengurt E, Walsh JH | title = Gastrin, CCK, signaling, and cancer | journal = Annual Review of Physiology | volume = 63 | issue =  | pages = 49–76 | year = 2001 | pmid = 11181948 | doi = 10.1146/annurev.physiol.63.1.49 }}
* {{cite journal | vauthors = Dockray GJ | title = Clinical endocrinology and metabolism. Gastrin | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 18 | issue = 4 | pages = 555–68 | date = December 2004 | pmid = 15533775 | doi = 10.1016/j.beem.2004.07.003 }}
* {{cite journal | vauthors = Anlauf M, Garbrecht N, Henopp T, Schmitt A, Schlenger R, Raffel A, Krausch M, Gimm O, Eisenberger CF, Knoefel WT, Dralle H, Komminoth P, Heitz PU, Perren A, Klöppel G | title = Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features | journal = World Journal of Gastroenterology | volume = 12 | issue = 34 | pages = 5440–6 | date = September 2006 | pmid = 17006979 | doi =  10.3748/wjg.v12.i34.5440}}
* {{cite journal | vauthors = Polosatov MV, Klimov PK, Masevich CG, Samartsev MA, Wünsch E | 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 | date = April 1979 | pmid = 463490 | doi =  }}
* {{cite journal | vauthors = 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 | date = April 1977 | pmid = 871064 | doi =  }}
* {{cite journal | vauthors = Higashimoto Y, Himeno S, Shinomura Y, Nagao K, Tamura T, Tarui S | title = Purification and structural determination of urinary NH2-terminal big gastrin fragments | journal = Biochemical and Biophysical Research Communications | volume = 160 | issue = 3 | pages = 1364–70 | date = May 1989 | pmid = 2730647 | doi = 10.1016/S0006-291X(89)80154-8 }}
* {{cite journal | vauthors = Pauwels S, Najdovski T, Dimaline R, Lee CM, Deschodt-Lanckman M | title = Degradation of human gastrin and CCK by endopeptidase 24.11: differential behaviour of the sulphated and unsulphated peptides | journal = Biochimica et Biophysica Acta | volume = 996 | issue = 1–2 | pages = 82–8 | date = June 1989 | pmid = 2736261 | doi = 10.1016/0167-4838(89)90098-8 }}
* {{cite journal | vauthors = Lund T, Geurts van Kessel AH, Haun S, Dixon JE | title = The genes for human gastrin and cholecystokinin are located on different chromosomes | journal = Human Genetics | volume = 73 | issue = 1 | pages = 77–80 | date = May 1986 | pmid = 3011648 | doi = 10.1007/BF00292669 }}
* {{cite journal | vauthors = Kariya Y, Kato K, Hayashizaki Y, Himeno S, Tarui S, Matsubara K | title = Expression of human gastrin gene in normal and gastrinoma tissues | journal = Gene | volume = 50 | issue = 1–3 | pages = 345–52 | year = 1986 | pmid = 3034736 | doi = 10.1016/0378-1119(86)90338-0 }}
* {{cite journal | vauthors = 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 | date = August 1969 | pmid = 5822140 | pmc = 1552899 | doi = 10.1136/gut.10.8.603 }}
* {{cite journal | vauthors = Bentley PH, Kenner GW, Sheppard RC | title = Structures of human gastrins I and II | journal = Nature | volume = 209 | issue = 5023 | pages = 583–5 | date = February 1966 | pmid = 5921183 | doi = 10.1038/209583b0 }}
* {{cite journal | vauthors = Ito R, Sato K, Helmer T, Jay G, Agarwal K | title = Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 15 | pages = 4662–6 | date = August 1984 | pmid = 6087340 | pmc = 391550 | doi = 10.1073/pnas.81.15.4662 }}
* {{cite journal | vauthors = Wiborg O, Berglund L, Boel E, Norris F, Norris K, Rehfeld JF, Marcker KA, Vuust J | title = Structure of a human gastrin gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 4 | pages = 1067–9 | date = February 1984 | pmid = 6322186 | pmc = 344765 | doi = 10.1073/pnas.81.4.1067 }}
* {{cite journal | vauthors = Kato K, Hayashizaki Y, Takahashi Y, Himeno S, Matsubara K | title = Molecular cloning of the human gastrin gene | journal = Nucleic Acids Research | volume = 11 | issue = 23 | pages = 8197–203 | date = December 1983 | pmid = 6324077 | pmc = 326575 | doi = 10.1093/nar/11.23.8197 }}
* {{cite journal | vauthors = Boel E, Vuust J, Norris F, Norris K, Wind A, Rehfeld JF, Marcker KA | title = Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 10 | pages = 2866–9 | date = May 1983 | pmid = 6574456 | pmc = 393933 | doi = 10.1073/pnas.80.10.2866 }}
* {{cite journal | vauthors = Kato K, Himeno S, Takahashi Y, Wakabayashi T, Tarui S, Matsubara K | title = Molecular cloning of human gastrin precursor cDNA | journal = Gene | volume = 26 | issue = 1 | pages = 53–7 | date = December 1983 | pmid = 6689486 | doi = 10.1016/0378-1119(83)90035-5 }}
* {{cite journal | vauthors = Koh TJ, Wang TC | title = Molecular cloning and sequencing of the murine gastrin gene | journal = Biochemical and Biophysical Research Communications | volume = 216 | issue = 1 | pages = 34–41 | date = November 1995 | pmid = 7488110 | doi = 10.1006/bbrc.1995.2588 }}
* {{cite journal | vauthors = 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 = The EMBO Journal | volume = 14 | issue = 2 | pages = 389–96 | date = January 1995 | pmid = 7530658 | pmc = 398093 | doi =  }}
* {{cite journal | vauthors = Rehfeld JF, Johnsen AH | title = Identification of gastrin component I as gastrin-71. The largest possible bioactive progastrin product | journal = European Journal of Biochemistry | volume = 223 | issue = 3 | pages = 765–73 | date = August 1994 | pmid = 8055952 | doi = 10.1111/j.1432-1033.1994.tb19051.x }}
* {{cite journal | vauthors = Varro A, Dockray GJ | title = Post-translational processing of progastrin: inhibition of cleavage, phosphorylation and sulphation by brefeldin A | journal = The Biochemical Journal | volume = 295 | issue = Pt 3 | pages = 813–9 | date = November 1993 | pmid = 8240296 | pmc = 1134634 | doi =  10.1042/bj2950813}}
{{Refend}}
 
== External links ==
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gastrin.html Overview at colostate.edu]
* [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/gi/gastrin.html Overview at colostate.edu]
* {{GeorgiaPhysiology|6/6ch4/s6ch4_14}}
* {{GeorgiaPhysiology|6/6ch4/s6ch4_14}}


 
{{Gastrointestinal physiology}}
{{Hormones}}
{{Hormones}}
{{Gastrointestinal physiology}}
{{Gastrointestinal hormones}}
{{Neuropeptides}}
{{Neuropeptides}}
{{Neuropeptidergics}}


[[Category:Peptide hormones]]
[[Category:Peptide hormones]]
[[Category:Gastric hormones]]
[[Category:Gastric hormones]]
[[Category:Digestive system]]
[[Category:Digestive system]]
[[Category:Endocrinology]]
[[Category:Cholecystokinin agonists]]
 
 
[[de:Gastrin]]
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[[es:Gastrina]]
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[[he:גסטרין]]
[[nl:Gastrine]]
[[ja:ガストリン]]
[[no:Gastrin]]
[[pl:Gastryna]]
[[pt:Gastrina]]
[[ru:Гастрин]]
[[sr:Гастрин]]
[[fi:Gastriini]]
[[sv:Gastrin]]
 
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Latest revision as of 15:29, 22 December 2018

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External IDsGeneCards: [1]
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SpeciesHumanMouse
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Gastrin
Identifiers
SymbolGastrin
PfamPF00918
InterProIPR001651
PROSITEPDOC00232

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

In humans, the GAS gene is located on the long arm of the seventeenth 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. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in posttranslational modification to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:

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: [citation needed]

Gastrin release is inhibited by:[4][5]

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. [citation needed]

Along with the above-mentioned function, gastrin has been shown 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 relaxes the pyloric sphincter, which increases the rate of gastric emptying.[6]
  • Plays a role in the relaxation of the ileocecal valve.[7]
  • Induces pancreatic secretions and gallbladder emptying.[8]
  • May impact lower esophageal sphincter (LES) tone, causing it to contract,[9] - although pentagastrin, rather than endogenous gastrin, may be the cause.[10]
  • Gastrin contributes to the gastrocolic reflex.

Factors influencing secretion

Physiologic

Gastric lumen
  • Stimulatory factors: dietary protein and amino acids (meat), 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 or gastrin-releasing peptide (GRP)
  • 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
Circulation

Pathophysiologic

Paraneoplastic

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. [citation needed]

In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria (low stomach acid secretion). 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.[11] Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H pylori infection.[12]

History

Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins,[13][14] and gastrins were isolated in 1964 by Hilda J. Tracy and Roderic Alfred Gregory at the University of Liverpool.[15] In 1964 the structure of gastrin was determined.[16]

References

  1. ↑ Lund T, Geurts van Kessel AH, Haun S, Dixon JE (May 1986). "The genes for human gastrin and cholecystokinin are located on different chromosomes". Human Genetics. 73 (1): 77–80. doi:10.1007/BF00292669. PMID 3011648.
  2. ↑ Blanco, Antonio; Blanco, Gustavo (2017), "Biochemical Bases of Endocrinology (II) Hormones and Other Chemical Intermediates", Medical Biochemistry, Elsevier, pp. 573–644, ISBN 9780128035504, retrieved 2018-11-02
  3. ↑ Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR, Wank SA (October 2010). "Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion". Proceedings of the National Academy of Sciences of the United States of America. 107 (41): 17791–6. doi:10.1073/pnas.1009078107. PMC 2955134. PMID 20876097.
  4. ↑ 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.
  5. ↑ Johnson LR (March 1984). "Effects of somatostatin and acid on inhibition of gastrin release in newborn rats". Endocrinology. 114 (3): 743–6. doi:10.1210/endo-114-3-743. PMID 6141932.
  6. ↑ Tortora, G. J., & Grabowski, S. R. (1996). Principles of anatomy and physiology. New York, NY: HarperCollins College. 14th Ed. Pg 906
  7. ↑ 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". Neurogastroenterology and Motility. 9 (4): 265–70. doi:10.1046/j.1365-2982.1997.d01-59.x. PMID 9430795.
  8. ↑ Valenzuela JE, Walsh JH, Isenberg JI (September 1976). "Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man". Gastroenterology. 71 (3): 409–11. PMID 950091.
  9. ↑ Castell DO (February 1978). "Gastrin and lower esophageal sphincter tone". Archives of Internal Medicine. 138 (2): 196. doi:10.1001/archinte.138.2.196. PMID 626547.
  10. ↑ Henderson JM, Lidgard G, Osborne DH, Carter DC, Heading RC (February 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.
  11. ↑ 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". Proceedings of the National Academy of Sciences of the United States of America. 95 (3): 1207–12. doi:10.1073/pnas.95.3.1207. PMC 18720. PMID 9448310.
  12. ↑ "Review Article: Strategies to Determine Whether Hypergastrinaemia Is Due to Zollinger-Ellison Syndrome Rather Than a More Common Benign Cause". www.medscape.com.
  13. ↑ Edkins JS (March 1906). "The chemical mechanism of gastric secretion". The Journal of Physiology. 34 (1–2): 133–44. doi:10.1113/jphysiol.1906.sp001146. PMC 1465807. PMID 16992839.
  14. ↑ Modlin IM, Kidd M, Marks IN, Tang LH (February 1997). "The pivotal role of John S. Edkins in the discovery of gastrin". World Journal of Surgery. 21 (2): 226–34. doi:10.1007/s002689900221. PMID 8995084.
  15. ↑ 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. PMC 1552180.
  16. ↑ Gregory H, Hardy PM, Jones DS, Kenner GW, Sheppard RC (December 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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