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Details for messenger / hormone: gastrin

EndoNet ID: ENH00076

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Synonyms

  • gastrin

General information

  • Gastrin stimulates the gastric mucosa (parietal cell) to produce and secrete hydrochloric acid.
  • All bioactive gastrin peptides are carboxyamidated and exist in nonsulfated and sulfated forms, due to O-sulfation of the tyrosyl residue (Tyr6), as counted from the COOH terminus. [1]
  • Gastrin activates many paracrine signalling pathways including release of somatostatin, activation of COX-2, shedding or induction of members of the EGF family, FGF-1, Reg and the chemokine IL-8. [2]
  • Gastrin stimulates the pancreas to secrete its digestive enzymes. [3]
  • Gastrin stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine. [3]
  • Gastrin synthesis and release is stimulated by aminoacids and peptides in the gastric lumen, and inhibited by gastric acid via the paracrine mediator somatostatin released from D-cells. [2]
  • Increased gastrin release in pernicious anaemia and after treatment with inhibitors of the H+/K+ ATPase. [2]
  • Gastrin acts via shedding of HB-EGF to stimulate proliferation. [2]
  • Gastrin also stimulates HB-EGF gene expression. [2]
  • Gastrin acts mainly via release of histamine from ECL cells, which then functions as a paracrine mediator in the gastric mucosa to stimulate parietal cells. [2]
  • Human progastrin is an 80-residue polypeptide that is cleaved by the prohormone convertases 1/3 and 2 and then C-terminally trimmed by carboxypeptidase E. Subsequent {alpha}-amidation by the amidation enzyme complex, peptidylglycine {alpha}-amidating monooxygenase, generates the acid stimulatory gastrins, gastrin-17 and gastrin-34. [4]

Classification

Hormone function

  • metabolism
    • nutrient supply

    Chemical classification

    • hormone
      • genome-encoded
        • gastrointestinal hormones
          • preprogastrin-derived peptides
            • non-classical gastrins

      Links to other resources

      UniProt P01350
      Ensembl ENST00000329402
      KEGG hsa:2520
      • Anatomical structure: D_cell

        • Co-localization of gastrin and CRH in D-cells was determined by immunocytochemistry. S.456 [5]
      • Anatomical structure: mucosa_of_gastric_wall

      • Anatomical structure: G_cell

        • Progastrin is synthesized in antral G cells and processed into a number of bioactive peptides, of which the heptadecapeptide gastrin-17 is the main product. [1]

        Influenced by:

        • PPAR-alpha
          in G_cell
          • PPARalpha agonists stimulate progastrin production. [6]
        • EGFR isoform a
          in G_cell
          • Activation of the canonical MAPK pathway by EGF stimulates gastrin gene expression via phosphorylation of Sp1. [2]
        • CaSR
          in G_cell
        • CCK-2
          in D_cell_of_gastrointestinal_tract
          • Gasrin secretion is inhibitted by gastric acid, probably via the paracrine mediator somatostatin [7]

      Targets

      CellCCK-1CCK-2
      alpha cell of islet of Langerhans Present
      Influences
      • glucagon
      cell of adrenal gland zona glomerulosa Present
      Influences
      • aldosterone
      Present
      Influences
      • aldosterone
      colon Present
      Phenotypes
      • induction of smooth muscle contraction
      Present
      Phenotypes
      • induction of smooth muscle contraction
      D cell Present
      Influences
      • somatostatin
      D cell of gastrointestinal tract Present
      Influences
      • somatostatin
      • gastrin
      digestive system Present
      Influences
      • somatostatin
      enterochromaffin like cell Present
      Phenotypes
      • positive regulation of smooth muscle proliferation
      Influences
      • histamine
      gallbladder Present
      Phenotypes
      • gastro-intestinal system smooth muscle contraction
      hypothalamus Present
      Phenotypes
      • negative regulation of appetite
      Present
      Phenotypes
      • negative regulation of appetite
      intestinal smooth muscle cell Present
      Phenotypes
      • induction of smooth muscle contraction
      Present
      Phenotypes
      • induction of smooth muscle contraction
      mucosa of small intestine Present
      Present
      neuron Present
      oxyntic cell of gastric gland Present
      Present
      Phenotypes
      • positive regulation of gastric acid secretion
      pancreas Present
      Phenotypes
      • mitogen activity
      • positive regulation of pancreatic juice secretion
      Influences
      • pancreatic alpha-amylase
      smooth muscle Present
      stomach Present
      Phenotypes
      • inhibition of gastric emptying
      zymogenic cell of gastric gland Present
      Reference