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.
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:
the presence of partially digestedproteins, especially amino 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 stimulates parietal cells of the stomach to secretehydrochloric 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 respond 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.[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 impact lower esophageal sphincter (LES) tone, causing it to contract,[14] - although pentagastrin, rather than endogenous gastrin, may be the cause.[15]
Factors influencing secretion of gastrin can be divided into 2 categories:[16]
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.
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 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.[17]
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.[18] Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H. pylori infection.[19]
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.
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Fritsch WP, Hausamen TU, Scholten T (April 1977). "[Gastrointestinal hormones. I. Hormones of the gastrin group]". Zeitschrift Fur 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.
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.
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.
