|, GAS, gastrin|
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.
In humans, the GAS gene is located on the long arm of the seventeenth chromosome (17q21).
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.
Gastrin is released in response to certain stimuli. These include:
Gastrin release is inhibited by:
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[failed verification] 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.
Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
Factors influencing secretion of gastrin can be divided into 2 categories:
In the Zollinger–Ellison syndrome, gastrin is produced at excessive levels, often by a gastirinoma 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.
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. Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H pylori infection.
Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, and gastrins were isolated in 1964 by Hilda Tracy and Roderic Alfred Gregory at the University of Liverpool. In 1964 the structure of gastrin was determined.