preprogastrin

Preprogastrin is the initial translation product of the gastrin gene and serves as the biosynthetic precursor to the secreted gastrin peptides. It is a larger, inactive polypeptide that contains an N-terminal signal peptide, which directs the nascent chain into the secretory pathway of the gastrointestinal tract.

Following synthesis, the signal peptide is cleaved to produce progastrin, an intermediate form that undergoes further proteolytic processing by prohormone convertases in the Golgi apparatus and secretory vesicles. This processing ultimately yields the secreted, bioactive gastrin peptides. The mature gastrins are typically C-terminally amidated peptides, with gastrin-34 and gastrin-17 being the most well-known active forms.

Gastrin is produced primarily by enteroendocrine G cells in the stomach antrum and duodenum, and to a lesser extent in other tissues. It stimulates gastric acid secretion by parietal cells, in part by promoting histamine release from enterochromaffin-like cells, which further enhances acid production, and it also supports mucosal growth.

Preprogastrin itself is not active, but the efficiency and pattern of its processing influence the levels and forms of gastrin produced. Aberrant processing can lead to accumulation of progastrin or other fragments, which in some contexts may have different biological effects, including associations with cellular proliferation in certain gastrointestinal diseases and cancers.

In summary, preprogastrin is the biosynthetic starting form of gastrin, ensuring proper trafficking through the secretory pathway before proteolytic processing yields the bioactive gastrin peptides that regulate gastric function and mucosal growth.