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 and then gastrin in various forms, primarily the following three:
the presence of partially digested proteins, especially amino acids, in the stomach. Aromatic amino acids are particularly powerful stimuli for gastrin release.
The presence of gastrin stimulates parietal cells of the stomach to secretehydrochloric acid /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. Along with the above-mentioned function, gastrin has been shown to have additional functions as well:
Stimulates parietal cell maturation and fundal growth.
Factors influencing secretion of gastrin can be divided into 2 categories:
Physiologic
Gastric lumen
Stimulatory factors: dietary protein and amino acids, hypercalcemia.
Inhibitory factor: acidity - 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 of the duodenum or the pancreas. To investigate for hypergastrinemia, a "pentagastrin test" can be performed. In autoimmune gastritis, the immune system attacks the parietal cells leading to hypochlorhydria. 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 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.
History
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.
