Gastrin binds tocholecystokinin 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 bypeptides in thelumen of the stomach.
Gastrin is a linearpeptide hormone produced byG cells of the duodenum and in thepyloric antrum of thestomach. It is secreted into the bloodstream. The encoded polypeptide is preprogastrin, which is cleaved by enzymes inposttranslational 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 theC-terminus end of gastrin.The numbers refer to theamino acid count.
the presence of partiallydigestedproteins, especiallyamino acids, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.[6]
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 stimulatesparietal cells of the stomach tosecretehydrochloric acid (HCl)/gastric acid. This is done both directly on the parietal cell and indirectly via binding ontoCCK2/gastrin receptors onECL cells in the stomach, which respond by releasinghistamine, which in turn acts in a paracrine manner on parietal cells stimulating them to secreteH+ ions. This is the major stimulus for acid secretion by parietal cells.[10]
Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
Stimulates parietal cell maturation and fundal growth.
May impactlower esophageal sphincter (LES) tone, causing it to contract,[14] - although pentagastrin, rather than endogenous gastrin, may be the cause.[15]
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 fromδ cells in the stomach, which inhibits gastrin and histamine release.
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.
In theZollinger–Ellison syndrome, gastrin is produced at excessive levels, often by agastrinoma gastrin-producing tumor, mostly benign of theduodenum or thepancreas. To investigate for hypergastrinemia high blood levels of gastrin, a "pentagastrin test" can be performed.[17]
In autoimmunegastritis, the immune system attacks theparietal cells leading tohypochlorhydria 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 andachlorhydria results leading to a loss ofnegative feedback on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals withmucolipidosis 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.[18] Additionally, elevated gastrin levels may be present in chronic gastritis resulting fromH. pylori infection.[19]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.PMID3011648.S2CID32216320.
^Blanco A, Blanco G (2017). "Chapter 26: Biochemical Bases of Endocrinology (II) Hormones and Other Chemical Intermediates.".Medical Biochemistry. Elsevier. pp. 573–644.doi:10.1016/b978-0-12-803550-4.00026-4.ISBN9780128035504.
^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.PMID1354190.
^Lindström E, Chen D, Norlén P, Andersson K, Håkanson R (March 2001). "Control of gastric acid secretion:the gastrin-ECL cell-parietal cell axis".Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology.128 (3):505–514.doi:10.1016/s1095-6433(00)00331-7.PMID11246041.
^Tortora GJ, Grabowski SR (1996).Principles of anatomy and physiology (14th ed.). New York, NY: HarperCollins College. p. 906.
^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):265–270.doi:10.1046/j.1365-2982.1997.d01-59.x.PMID9430795.S2CID31858033.
^Castell DO (February 1978). "Gastrin and lower esophageal sphincter tone".Archives of Internal Medicine.138 (2): 196.doi:10.1001/archinte.138.2.196.PMID626547.
^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):226–234.doi:10.1007/s002689900221.PMID8995084.S2CID28243696.
Polosatov MV, Klimov PK, Masevich CG, Samartsev MA, Wünsch E (April 1979). "Interaction of synthetic human big gastrin with blood proteins of man and animals".Acta Hepato-Gastroenterologica.26 (2):154–159.PMID463490.
Fritsch WP, Hausamen TU, Scholten T (April 1977). "[Gastrointestinal hormones. I. Hormones of the gastrin group]".Zeitschrift für Gastroenterologie.15 (4):264–276.PMID871064.
Higashimoto Y, Himeno S, Shinomura Y, Nagao K, Tamura T, Tarui S (May 1989). "Purification and structural determination of urinary NH2-terminal big gastrin fragments".Biochemical and Biophysical Research Communications.160 (3):1364–1370.doi:10.1016/S0006-291X(89)80154-8.PMID2730647.
Pauwels S, Najdovski T, Dimaline R, Lee CM, Deschodt-Lanckman M (June 1989). "Degradation of human gastrin and CCK by endopeptidase 24.11: differential behaviour of the sulphated and unsulphated peptides".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.996 (1–2):82–88.doi:10.1016/0167-4838(89)90098-8.PMID2736261.
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Kariya Y, Kato K, Hayashizaki Y, Himeno S, Tarui S, Matsubara K (1986). "Expression of human gastrin gene in normal and gastrinoma tissues".Gene.50 (1–3):345–352.doi:10.1016/0378-1119(86)90338-0.PMID3034736.
Kato K, Himeno S, Takahashi Y, Wakabayashi T, Tarui S, Matsubara K (December 1983). "Molecular cloning of human gastrin precursor cDNA".Gene.26 (1):53–57.doi:10.1016/0378-1119(83)90035-5.PMID6689486.
Koh TJ, Wang TC (November 1995). "Molecular cloning and sequencing of the murine gastrin gene".Biochemical and Biophysical Research Communications.216 (1):34–41.doi:10.1006/bbrc.1995.2588.PMID7488110.
